# Major Milestones Against Cancer

ASCO’s Cancer Progress Timeline is an interactive, data-rich resource that provides an historical overview of major advances in cancer that have led to better outcomes and quality of life for patients. More than 400 milestones spanning 170 years are chronicled in the Timeline—from the advent of general anesthesia opening the door for cancer surgery in the mid-1800s to the first gene therapy for cancer approved by the Food and Drug Administration in 2017.

The Timeline highlights some of the most important advances across cancer care and research. Many of these milestones were supported by federal research funding, and nearly all of them are the result of rigorously conducted clinical trials, made possible by the participation of thousands of individuals with cancer. ASCO’s federally funded research badge is featured on milestones that stemmed from research funded at least in part by the National Cancer Institute or other federal agencies.

The Cancer Progress Timeline is a historical overview of ground-breaking advances in cancer research and care that have improved the outlook for patients and led to a better quality of life. With more than 400 milestones, the Timeline spans 170 years, including advances such as the advent of general anesthesia and its use for cancer surgery in the mid-1800s, the signing of the National Cancer Act into law in 1971, and recent breakthroughs in immunotherapy.

The Timeline features a chronology of Major Milestones of ground-breaking advances across cancer care and research. In addition, there are timelines that detail practice-changing advances for common cancer types and types of care. Many of the advances in the Cancer Progress Timeline have also been featured in ASCO’s Clinical Cancer Advances report, which tells the story of each year’s most influential research.

Logo for National Cancer Act’s 50th anniversary2021 marked the 50th anniversary of the National Cancer Act, which opened a new era of cancer research in the United States. It led to a major expansion of funding for cancer research and paved the way for the next five decades of progress and advances in cancer prevention, screening, and treatment. Many of the advances in the Progress Timeline are directly attributable or can trace their development, to federal research funding. These advances are marked by ASCO’s federally funded research badge.

## 2020

### First-In-Class Drug Reduces Need for Transfusion in Patients With Lower-Risk MDS

One of the most common features of myelodysplastic syndromes (MDS) is anemia. Patients with lower risk MDS who are anemic are typically treated with red blood cell transfusions and erythropoietin-stimulating agents and can require transfusions for long periods of time. However, not all patients are able to tolerate these treatments. Luspatercept is a new type of drug that helps red blood cell precursors become mature red blood cells, increasing the red blood cell count. More patients in the phase III MEDALIST trial (ClinicalTrials.gov identifier: NCT02631070) who received luspatercept (38%) no longer required transfusions for 8 weeks compared with those in the placebo arm (13%). The findings of this trial led to the approval of luspatercept by the FDA for patients with lower-risk myelodysplastic syndromes with ringed sideroblasts. This class of drugs fills a significant need among patients with MDS.

Lancet. 383:2239-2252, 2014

N Engl J Med 2020; 382:140-151

FDA Approval

## 2019

### Long-term Data Proves HPV Vaccine Is Effective Against Infection and Cervical Intraepithelial Neoplasia

The first vaccine for human papillomavirus (HPV) was licensed in 2006 with the aim of preventing infections that can lead to cervical cancer and anogenital warts later in life. Today nearly 100 countries have instituted HPV vaccination programs. In a 2019 analysis of real-world data, researchers found that the prevalence of two high-risk HPV strains (16 and 18) dropped by 83% among females age 13-19 years and by 66% in young women age 20-24 years in the 5-8 years after the introduction of HPV vaccination. The analysis included 40 trials in high-income countries between 2014 and 2018. Decreases in prevalence of HPV 16 and 18 were also seen for women age 25-29 years (most of whom are unvaccinated in the general population), as well as decreases for HPV 31, 33, and 45 for females age 13-24 years. In addition, after 5-9 years of vaccination, grade 2+ cervical intraepithelial neoplasia (CIN2+) decreased by 51% among screened girls aged 15–19 years and by 31% among women aged 20–24 years.

The Lancet 2019;394:497-509

### Targeted Therapy Ribociclib Added to Endocrine Therapy Improves Survival in Young Women with Certain Types of Breast Cancer

The combination of the CDK4/6 inhibitor ribociclib with endocrine therapy provided an overall survival advantage for pre- and perimenopausal women with advanced HR+, HER2- breast cancer, compared to standard endocrine therapy plus placebo. Results from the MONALEESA-7 trial showed 42-month survival with ribociclib of 70.2%, compared with 46% for women who received placebo plus standard endocrine treatment. The treatment combination is an important step forward for the treatment of younger women with this disease, who tend to have more aggressive disease with worse survival than those who are postmenopausal.

N Engl J Med 2019; 381: 307-16

### First FDA-Approved Combination and Chemotherapy-Free Treatment Regimen Improves Progression-Free Survival for Patients With Slow-Growing Forms of Non-Hodgkin Lymphoma

Follicular lymphoma and marginal zone lymphoma are the most common types of non-Hodgkin lymphoma (NHL). Lenalidomide plus rituximab is the first FDA-approved combination treatment regimen for patients with these lymphomas that does not include chemotherapy. The combination’s 2019 FDA approval was based on the results of a phase-III randomized trial of the regimen conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Compared with placebo plus rituximab, the lenalidomide/rituximab combination roughly halved the risk of disease progression, with median progression-free survival of 39.4 months versus 14.1 months with placebo.

J Clin Oncol 2019;37:1188-99

## 2018

### Maintenance Olaparib Extends Progression Free Survival in Patients With Advanced BRCA-Mutated Ovarian Cancer

Poly (ADP-ribose) polymerase, or PARP inhibitors, represent a major treatment advance in ovarian cancer. These enzymes promote cancer cell death by interfering with DNA replication in cancers that have faulty DNA damage-repair genes, such as BRCA1/2. In this phase-III trial, women with newly diagnosed advanced-stage BRCA-mutated ovarian cancer received maintenance therapy with the PARP inhibitor olaparib following surgery and chemotherapy. Women treated with olaparib had a 70% lower risk of disease progression or death compared to no maintenance treatment. Not only did these results lead to FDA approval of olaparib for this indication, they represent a big step forward in treating patients with this type of cancer.

N Engl J Med 2018;379:2495-2505

### Treatment targets BRCA mutations in breast cancer

Findings from a large clinical trial of women with advanced, germline BRCA mutation-related breast cancer show that the PARP inhibitor olaparib (Lynparza) lowers the risk of cancer progression, with fewer side effects, compared to standard chemotherapy. Based on these data, olaparib is approved for this use by FDA, marking the first time any drug has been approved to treat certain patients with a BRCA gene mutation who have metastatic breast cancer. Up to 3% of all breast cancers are related to inherited changes in the BRCA1 and BRCA2 genes, which affect a cell’s ability to repair damaged DNA. PARP inhibitors further block DNA repair in cancer cells, which helps slow or stall tumor growth.

N Engl J Med 2017;377:523-533

FDA Approval

### Combination therapy offers first effective treatment for Anaplastic Thyroid Cancer in nearly 50 years

The combination of trametinib (Mekinist) and dabrafenib (Tafinlar) shows a strong and durable response in a single-arm phase II study of patients with anaplastic thyroid cancer (ATC) with BRAF V600E mutation and no satisfactory locoregional treatment options. Based on the results, the therapy is approved for the treatment of patients with locally advanced or metastatic ATC. The combination is the first therapy approved for ATC in nearly 50 years. Combination treatment with trametinib and dabrafenib become the standard of care for patients with ATC with tumors that have a BRAF mutation.

J Clin Oncol 2018;36:7-13

FDA Approval

### Immunotherapy Combination Extends Survival for Renal Cell Carcinoma

Nivolumab (Opdivo) is a programmed death 1 (PD-1) immune checkpoint inhibitor antibody; ipilimumab (Yervoy) is an anti–cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody. While both treatments are checkpoint inhibitors, they work in different but complementary ways. Results from the phase III CheckMate 214 trial shows that the combination of these two treatments provides a survival benefit for patients who were previously untreated for advanced renal cell carcinoma with intermediate- and poor-risk disease, when compared with standard treatment. The findings lead to the approval of this combination therapy — the first immunotherapy regimen — for kidney cancer.

N Engl J Med 2018;378:1277-1290

FDA Approval

### 21-Gene Expression Assay Guides Choice of Adjuvant Therapy for Certain Patients with Breast Cancer

A 21-gene-basedtest (Oncotype DX) predicts risk of recurrence and guides adjuvant therapy for women with low and high risk of recurrence of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2) negative, lymph node-negative breast cancer. Women at low risk for recurrence can receive endocrine therapy alone, while those at high risk receive chemoendocrine therapy. However, it is unclear how to treat women with intermediate risk. The TAILORx trial shows that for women with test results indicating an intermediate risk of recurrence, chemotherapy is no longer needed as endocrine therapy alone results in comparable survival.

N Engl J Med 2018;379:111-121

### Sodium Thiosulfate Helps Reduce Risk of Cisplatin-Induced Hearing Loss

While cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma, cisplatin treatment can result in serious and irreversible hearing loss. The use of sodium thiosulfate following cisplatin treatment roughly halves the risk of hearing loss in a study of more than 100 patients with hepatoblastoma from 1 month to 18 years of age. Event-free and overall survival at 3 years are comparable with and without the addition of sodium thiosulfate.

N Engl J Med 2018;378:2376-2385

### First Immunotherapy Approved for Metastatic Triple-Negative Breast Cancer

Atezolizumab in combination with chemotherapy is not only the first immunotherapy approved for breast cancer, but also an important advance for patients with advanced triple-negative breast cancer, which has an extremely poor prognosis. The FDA approval of the immunotherapy combination( PD-L1 targeted therapy atezolizumab with nanoparticle albumin-bound nab paclitaxel) was largely based on the results of the IMpassion130 trial. Progression-free survival was improved among patients with tumors that expressed PD-L1 who received atezolizumab in combination with nab paclitaxel.

N Engl J Med 2018;379:2108-21

### Lower Intensity Methotrexate Produces Highest Cure Rates for Pediatric Patients with T-ALL

A less toxic treatment regimen of the anti-cancer drug methotrexate resulted in the best outcomes ever reported for children and adolescents with T-cell acute lymphoblastic leukemia (T-ALL). In a federally-funded trial, the regimen showed a 5-year disease-free survival rate of 91.5% and overall survival rate of 93.7%. In comparison, the historical overall survival rate for T-ALL was approximately 81% based on earlier clinical trials in this patient population.

J Clin Oncol 2018;36:2926-34

### Immunotherapy/Chemotherapy Combination Approved for Extensive SCLC

The 2019 FDA approval of the immunotherapy atezolizumab in combination with chemotherapy represents a major advance in the treatment of extensive small cell lung cancer. The approval was based on the results of the IMpower 133 study, which showed significantly longer survival with the addition of atezolizumab to carboplatin and etoposide chemotherapy. The combination therapy has become the standard of care for extensive-stage small cell lung cancer in the United States.

N Engl J Med 2018; 379:2220-9

## 2017

### First gene therapy for cancer

In a landmark trial, the chimeric antigen receptor-modified T cell (CAR-T) therapy tisagenlecleucel (Kymriah) causes complete remissions in a majority of young patients with B-cell acute lymphoblastic leukemia (ALL) that progressed despite previous treatment with standard therapies. Soon after, tisagenlecleucel becomes the first gene therapy to be approved by the FDA.

CAR-T therapy works by genetically modifying the patient’s own immune T cells to target a specific cancer protein and ultimately trigger the cancer cell’s destruction. Importantly, this “living therapy” needs to be given to the patient only once, because CAR T cells continue to multiply in the patient’s body, so the anticancer effects of CAR T cells persist and can even increase over time.

FDA News Release; FDA approval brings first gene therapy to the United States

Clinical Lymphoma, Myeloma & Leukemia Blood 2017; 17 (Suppl. 2): S263–S264

Blood 2016; 128: 221

European Hematology Association 2017; 181763: S476

N Engl J Med 2014; 371: 1507-1517

### First therapy introduced to treat cancer based on tumor genomics alone

Researchers demonstrate the efficacy of the immune checkpoint inhibitor pembrolizumab (Keytruda) for the treatment of patients with 12 different solid tumor types with high microsatellite instability, a signature of DNA mismatch repair deficiency. Pembrolizumab results in long-lasting tumor shrinkage in a significant portion of patients with these tumor types. Based in part on these results, the FDA grants accelerated approval to pembrolizumab (KEYTRUDA) for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. This approval marks a milestone in precision oncology, when for the first time a patient can be treated on the basis of the tumor’s genomics, instead of its location in the body.

Science 2017; 357(6349):409-413

FDA Approval

### Integrating patient-reported outcomes into routine cancer care improves survival

A large, randomized trial demonstrates for the first time that capturing patient-reported outcomes on an ongoing basis using a web-based tool helps patients with advanced cancer live several months longer, compared to standard care. The web-based tool enables patients to report common symptoms in real time and triggers alerts to clinicians if symptoms worsen. When appropriate, clinicians take action to relieve symptoms, such as lowering chemotherapy dosing or changing supportive care plans. The study demonstrates how newer technologies aimed at improving communications between patients and their health care teams can have a meaningful impact on survival and quality of life. This development spurs greater focus on integrating similar tools into routine cancer care.

JAMA 2017;318:197-198

### Lu 177 Dotatate Delivers Targeted Radiation to Somatostatin Receptor-positive Midgut Neuroendocrine Tumors

Lutetium 177 dotatate is a compound that combines a radioactive isotope with a somatostatin (growth hormone-inhibiting hormone) analog. This combination makes it possible to deliver radiation directly to tumor cells in patients with advanced, progressive, somatostatin receptor-positive midgut neuroendocrine tumors. The results of the NETTER-1 trial demonstrate improved response and longer progression-free survival with Lu 177 dotatate compared with standard treatment. Based on this data, the FDA approvedLu 177 Dotatate (Lutathera) for the treatment of adults with this type of tumor in the midgut, foregut, or hindgut.

N Engl J Med 2017;376:125-135

FDA Approval

## 2016

### Pembrolizumab extends NSCLC survival, with fewer side effects

Studies find that pembrolizumab (Keytruda) improves survival and causes fewer side effects than standard chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) and high levels of PD-L1 protein in the tumor. These trials include patients who were newly diagnosed and previously treated with other therapies, leading the FDA to approve the drug for both populations of patients. These approvals establish a new treatment paradigm for this type of lung cancer, with immunotherapy becoming the preferred treatment over chemotherapy regimens for PD-L1-positive cancers.

N Engl J Med 2016; 375:1823-1833

Lancet 2016; 387(10027): 1540–1550

FDA; Pembrolizumab (KEYTRUDA) Checkpoint Inhibitor

The FDA approves atezolizumab (Tecentriq) for treatment of advanced urothelial carcinoma, the most common form of bladder cancer. With this approval, atezolizumab becomes the first new bladder cancer treatment in 30 years and the first PD-L1 immune checkpoint inhibitor approved for any use. The approval follows an early clinical trial in which atezolizumab rapidly shrank tumors in patients with previously treated advanced urothelial cancer, particularly those with high levels of PD-L1 in the tumor and immune cells.

FDA News Release; FDA Approves New, Targeted Treatment for Bladder Cancer

Lancet 2016; 387(10031):1909-1920

### Childhood cancer survivors living longer and healthier

A federally funded analysis of over 34,000 five-year childhood cancer survivors shows significant gains in long-term survival over three decades, owing to steady refinements in treatment. The rate of death from any cause within 15 years of childhood cancer diagnosis declined by half (from 12% to 6%) among survivors treated in the 1990s compared to those treated in the 1970s. While treatment advances played a major role, reductions in treatment-related health complications likely had the greatest impact on long-term survival. This includes lower dose of radiation for certain cancers and less use of anthracycline chemotherapy. These advances helped make it possible for more than 400,000 childhood cancer survivors to be alive today in the United States.

N Engl J Med 2016; 374:833-842

NCI; Childhood Cancer Survivor Study: An Overview

## 2015

### A new class of breast cancer treatment introduced

2015-2016

Palbociclib (Ibrance) becomes the first in a new class of medicines called cyclin-dependent kinase (CDK) inhibitors, which block key proteins that control cell division. In clinical trials, addition of palbociclib to standard hormone therapy extended the time until the cancer worsened by a median of 11 months when given as initial therapy and by about 5 months for women with previously treated cancer. In 2015, the FDA grants accelerated approval to palbociclib in combination with letrozole (Femara) as initial hormone-based therapy in post-menopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. In 2016, the FDA grants accelerated approval to palbociclib with fulvestrant (Faslodex) to treat advanced breast cancer that worsens following initial hormone therapy.

Lancet Oncology 2016; 17(4): 425-439

N Engl J Med 2016; 375:1925-1936

FDA; Palbociclib (IBRANCE Capsules)

### Three immunotherapies introduced for most common type of lung cancer

Three new immunotherapies are approved by the FDA for patients with advanced non-small cell lung cancer (NSCLC) that worsened during or following chemotherapy. In clinical trials, the three drugs, nivolumab (Opdivo), atezolizumab (Tecentriq), and pembrolizumab (Keytruda), were each shown to extend survival and cause fewer severe side effects than chemotherapy. These treatments target the so-called immune checkpoint proteins PD-1 and PD-L1, respectively, helping the immune system fight cancer.

N Engl J Med. 2015 Jul 9;373(2):123-35

FDA News Release; FDA Expands Approved Use of Opdivo to Treat Lung Cancer

N Engl J Med 2015; 372(21): 2018-2028

N Engl J Med 2016; 375:1823-1833

FDA News Release; FDA Approves Keytruda for Advanced Non-small Cell Lung Cancer

Lancet 2016; 387(10030): 1837–1846

FDA; Atezolizumab (TECENTRIQ)

## 2014

### Four new drugs transform CLL treatment

In a span of eight months, the FDA approves four new treatments for chronic lymphocytic leukemia (CLL), a blood cancer that most commonly develops in older adults. Obinutuzumab (Gazyva) and ofatumumab (Arzerra), approved as initial treatments for CLL, delay cancer worsening by about a year when given with chemotherapy. Targeted drugs idelalisib (Zydelig) and ibrutinib (Imbruvica) were approved for use in patients with CLL that became resistant to or relapsed after standard treatment. In clinical trials, both slowed cancer worsening and ibrutinib also helped patients live longer.  All four new therapies are easier for patients to tolerate than prior therapies, making treatment possible for more patients than ever.

NCI; FDA Approval for Obinutuzumab

N Engl J Med 2014; 370:1101-1110

NCI; FDA Approval for Ofatumumab

N Engl J Med 2014; 371:213-223

NCI; FDA Expanded Approved Use of Ibrutinib

N Engl J Med 2014;370(11): 997-1007

NCI; FDA Approval for Idelalisib

### FDA approves two immunotherapies for melanoma

FDA grants accelerated approval to pembrolizumab (Keytruda) and nivolumab (Opdivo) for patients with advanced melanoma that cannot be removed with surgery who no longer respond to other treatments.

These therapies, known as “immune checkpoint inhibitors,” work by blocking a pathway called PD-1, that prevents the body’s immune system from attacking cancer cells.

Approval comes following research showing that the therapies shrank tumors in up to 40% of patients. In one clinical trial, nivolumab extended survival compared to targeted therapy for patients with BRAF mutations.

Lancet 2014; 384(9948): 1109–1117

Lancet Oncology 2015; 16(4): 375–384

JCO 2014; 32(10): 1020-1030

N Engl J Med 2015; 372: 320-330

## 2013

### Potential new approach to treating childhood leukemia found

An early clinical trial shows that a new approach called chimeric antigen receptor-modified T cell (CAR-T) therapy led to complete remission of acute lymphoblastic leukemia (ALL) that had not responded to previous aggressive treatment in two children. This is the first report on the use of CAR T-cell therapy in patients with ALL.

CAR-T therapy works by genetically modifying the patient’s own immune T cells to target a specific cancer protein.

New England Journal of Medicine

## 2011

### Aromatase inhibitors cut breast cancer risk in postmenopausal women

2011-2014

A large Phase III trial shows for the first time that exemestane (Aromasin) – part of a group of drugs called aromatase inhibitors – greatly lowers the chance of developing invasive breast cancer in postmenopausal women who are at a high risk for breast cancer. This includes women with BRCA gene mutations, as well as other risk factors. In 2014, another aromatase inhibitor, anastrozole (Arimidex), was shown to lower the risk of breast cancer by nearly 50% over five years.

Two other drugs, tamoxifen (Nolvadex) and raloxifene (Evista), are also FDA-approved for breast cancer prevention in women at high risk for the disease Aromatase inhibitors work differently, however, and tend to carry milder side effects.

N Engl J Med 2011; 364:2381-2391

Lancet 2014; 383(9922): 1041–1048

## 2010

### Record number of Americans surviving cancer – nearly 14 million

The National Cancer Institute and the American Cancer Society report that the number of cancer survivors in the U.S. increased to an all-time high of 13.7 million. This represents a more than four-fold increase since 1971 (when just 3 million survivors were alive). By 2022, the number of survivors is expected to reach 18 million. The report highlights major progress in treatment that has led to improved survival rates, as well as the need to address the long-term health effects of cancer, and cancer treatment, among survivors.

CDC MMWR: Cancer Survivors

### New prohibitions on indoor tanning after it’s declared carcinogenic

2009-2017

In 2009, the International Agency for Research on Cancer, a working group of the World Health Organization, declared that UV-emitting tanning devices are “carcinogenic to humans.”

Between 2011 and 2017, several new pieces of legislation are enacted to restrict the use of indoor tanning, starting with a new California law prohibiting indoor tanning to people under the age of 18. Fourteen other states and the District of Columbia subsequently follow suit.  In 2014, the U.S. Food & Drug Administration issues an order requiring all indoor tanning devices to carry a visible black-box warning against use before age 18, and it reclassifies indoor tanning devices from a low to a moderate risk, allowing the agency greater control over the devices. Policy changes continue in Australia, where nearly all states enact bans on indoor tanning in 2015.

International Agency for Research on Cancer; Sunbeds and UV Radiation

NCSL; Indoor Tanning Restrictions for Minors

FDA Code of Regulations Title 21 2017

Queensland Government Statement on Indoor Tanning

Lancet Oncology 2009; 10:751-752

### Adding palliative care to standard chemotherapy improves survival for advanced lung cancer patients

A head-to-head trial shows that patients who received standard chemotherapy along with palliative care (specialized treatment to address the symptoms of cancer, but not treat the disease) immediately after their diagnosis with advanced lung cancer lived three months longer and had a higher quality of life than patients who had chemotherapy alone. Patients who received the combination approach were also less likely to undergo aggressive therapy at the end of life, such as resuscitation. The results demonstrate the potential for palliative care to no only improve quality of life, but to extend patients’ lives as well.

Cancer.Net; Lung Cancer - Non-Small Cell: Treatment Options

N Engl J Med 2010; 363: 733-42

### First drug shown to improve survival for patients with advanced melanoma

In a Phase III study, the targeted drug ipilimumab (Yervoy) – which boosts a specific component of the immune system – is found to improve survival and delay disease progression in patients whose advanced melanoma progresses despite other therapies. The drug is approved for this use in early 2011.

Soon after, a second trial finds that treatment using a combination of ipilimumab and dacarbazine (a chemotherapy drug commonly used in melanoma) extends survival compared to dacarbazine treatment alone.

Cancer.Net; Melanoma: Treatment Options

N Engl J Med 2010; 363: 711-23

N Engl J Med 2011; 364: 2517-26

### CT scanning reduces lung cancer deaths among heavy smokers

Results from a large clinical trial show that annual screening with low-dose spiral CT (LDCT) scans reduces the risk of lung cancer death by 20 percent, compared to annual chest X-rays, in current and former heavy smokers.

The National Lung Screening Trial, funded by the National Cancer Institute, compared LDCT scanning to standard chest X-rays in this group of people at high risk for developing lung cancer. This finding marks the first-ever lung cancer screening approach that has been shown to reduce lung cancer mortality. The debate about the appropriate use of LDCT screening for lung cancer among the general population, however, continues.

Cancer.Net; Expert Perspective from ASCO on the Results of the National Lung Screening Trial

N Engl J Med 2011; 365: 395-409

## 2009

### Major studies report conflicting results about benefits of PSA testing

The proper role of PSA testing remains uncertain after large, randomized trials provide conflicting results on whether routine testing reduces deaths from prostate cancer. Initial results from two studies indicate that PSA testing has minimal, if any, effect on overall survival and leads to the over-diagnosis and treatment of slow-growing cancers that are unlikely to be life-threatening. A third study finds that PSA testing reduces the risk of prostate cancer death in some men by 40 percent. Given the conflicting evidence, leading medical societies urge men to discuss the risks and benefits of screening with their doctors.

Cancer.Net; Prostate Cancer: Risk Factors and Prevention

N Engl J Med 2009; 360: 1310-19

N Engl J Med 2009; 360: 1320-28

## 2006

### First vaccine approved to prevent cervical cancer

The FDA approves the first vaccine to prevent infection with two high-risk strains of the human papillomavirus (HPV16 and HPV18) that are known to cause about 70 percent of all cervical cancers. The vaccine, called Gardasil, is approved for girls and young women aged 9 to 26, based on a clinical trial showing that the vaccine was safe and was 100 percent effective against these types of HPV, and those that cause genital warts, for at least four and a half years after vaccination. A second vaccine, Cervarix, is approved in 2009 to prevent infection against the cancer-causing HPV strains in young women aged 10 to 25. Gardasil is later approved to prevent additional HPV-related diseases in children and young adults aged 9 to 26, including vaginal, vulvar and anal cancers in females, and anal cancer and genital warts in males. Studies have also linked HPV infection to head and neck cancers, suggesting that the vaccine may help prevent these cancers as well.

Cancer.Net; HPV and Cancer

Lancet Oncology 2005; 6(5): 271-78

N Engl J Med 2007; 356: 1928-43

## 2005

### Two targeted drugs approved for advanced colon cancer

The drugs cetuximab (Erbitux) and panitumumab (Vectibix) are approved to treat colon cancer that has spread to other parts of the body (metastatic disease). These drugs attack tumors that express the epidermal growth factor receptor (EGFR) protein, which is involved in cancer cell growth. Later, a coordinated analysis of multiple studies shows that cetuximab and panitumumab are effective only in patients with the normal form of a gene known as KRAS. This discovery helps physicians ensure that the drugs are used only for patients who stand to benefit, while eliminating unnecessary treatment and costs for patients who will not.

N Engl J Med 2008; 359: 1757-1765

Journal of Oncology Practice 2009; 5(2): 71-72

### Research sheds light on long-term health problems of cancer survivors

In the 1990s, researchers begin a major study of the long-term effects of cancer and its treatment, focusing on survivors of childhood cancer. In 2005, the Childhood Cancer Survivors Study reports that survivors’ risk of long-term health problems – including heart problems, second cancers and scarring of the lungs – was five times greater than that of their healthy siblings. Similar results have been found for survivors of other cancers with high cure rates, such as testicular cancer.

The results are helping oncologists and primary care providers monitor and better manage the long-term health of the millions of cancer survivors alive today.

Cancer.Net; Survivorship

NCI: Late Effects of Childhood Cancer

JNCI 2005; 97(18): 1354-65

### U.S. launches effort to map cancer genomes

The National Cancer Institute and the National Human Genome Research Institute team up to launch The Cancer Genome Atlas project. In its initial phase, the project aims to develop a comprehensive atlas of the genomes of three common cancers – lung, ovarian, and glioblastoma, a form of brain cancer. By gaining a deeper understanding of the genetic pathways involved in the development and growth of these cancers, researchers hope to identify molecular targets that can guide development of effective new treatment.

The Cancer Genome Atlas; Pilot Project

Nature 2008; 455: 1069-75

## 2004

### Adjuvant therapy proven effective in lung cancer

In findings that quickly change the standard of care, clinical trials show that giving chemotherapy after surgery dramatically improves survival for patients with early-stage non-small cell lung cancer, the most common form of the disease. Previously, chemotherapy was considered to be largely ineffective for lung cancer. These study results demonstrate that adjuvant chemotherapy could have an equal or greater impact on survival in lung cancer as it does in breast or colon cancer.

Cancer.Net; Lung Cancer - Non-Small Cell: Treatment Options

N Engl J Med 2004; 350: 351-60

N Engl J Med 2005; 352: 2589-97

### FDA approves first “anti-angiogenic” drug, bevacizumab

Bevacizumab (Avastin) is the first of a new generation of targeted drugs, called anti-angiogenics, that attack cancer by blocking the growth of blood vessels that tumors needs to grow. First approved to treat colorectal cancer, in 2004, the drug has since become an important treatment for patients with advanced lung, ovarian and kidney cancers, and for certain brain tumors, who have few other effective options.

N Engl J Med 2004; 350: 2335-42

Lancet 2007; 370(9605): 2103-11

## 2003

### First targeted drugs for lung cancer attack “EGFR” receptor

The FDA approves two new targeted treatments for advanced, non-small cell lung cancer, gefitinib (Iressa) and erlotinib (Tarceva). Both drugs target the epidermal growth factor receptor (EGFR), a protein on cell surfaces that is involved in driving lung cancer growth and spread. Approval is based on data showing that erlotinib extends survival in patients with advanced lung cancer – a rare finding for any treatment – and that gefitinib delays the time before a patient’s cancer progresses. Around the same time, studies show that the drugs only work for patients with specific mutations in the EGFR protein. These mutations are found most often in lung cancer patients who never smoked.

To date, the two drugs are approved only for certain patients whose cancer no longer responds to other therapies. But recent studies indicate that for people with the relevant EGFR mutations, the drugs could also be valuable first-line treatment options.

Lancet 2005; 366(9496): 1527-37

N Engl J Med 2010; 362: 2380-88

N Engl J Med 2009; 361: 947-957

### Obesity pinpointed as cause of many cancer deaths

An important prospective analysis involving nearly 1 million Americans reports that obesity could account for up to 20 percent of U.S. cancer deaths. Obesity is linked to a higher risk of death from liver cancer, along with several other cancer types. The researchers also estimate that 90,000 cancer-related deaths could be prevented annually if Americans maintained a healthy weight.

As obesity becomes more prevalent, researchers project that deaths from liver cancer and other forms of the disease will rise as well.

N Engl J Med 2003; 348: 1625-38

### Scientists decode the human genome

Scientists announce that they have successfully mapped the 3 billion DNA letters in the human genome. This marks the completion of the Human Genome Project, an unprecedented international collaboration between researchers in the U.S. in and six other countries, funded primarily by the U.S. government. Results of the 13-year effort are made freely available to scientists around the world, paving the way for research to identify the genetic defects that fuel cancer, and for new ways of screening for and treating the disease.

Nature 2003; 422: 835-47

Human Genome Project Informative Archive 1990-2003

## 2002

### Doubling of U.S. biomedical research budget expands cancer research

Beginning in 1998, President Bill Clinton and Congressional leaders enact a series of large, annual budget increases for the National Institutes of Health, doubling the agency’s biomedical research efforts over the next five years. The new investments accelerate the pace of cancer research in the lab and in the clinic, leading to important advances over the next decade. More recently, however, federal support for cancer research has declined in real terms, potentially slowing the pace of progress against the disease.

Office of Legislative Policy and Analysis: Legislative Chronology

New York Times; Government Ready to Boost Spending for Biomedicine

## 2001

### Imatinib found highly effective against rare gastrointestinal tumor

Just weeks after being approved to treat chronic myelogenous leukemia, the targeted drug imatinib is shown to be effective against a rare abdominal tumor called GIST (gastrointestinal stromal tumor). Prior to imatinib, available drug treatments had little effect on GIST tumors. Imatinib works like a “circuit breaker” to block enzymes that can send faulty signals to trigger tumor cell growth. In GIST, it blocks the growth signal of a gene called c-Kit.

N Engl J Med 2002; 347: 472-80

### New targeted therapy transforms treatment for rare leukemia

The FDA approves imatinib (Gleevec) after just three months of review – the fastest approval in FDA history – based on data showing the drug halted the growth of chronic myelogenous leukemia (CML) in the majority of patients. Imatinib is the first drug proven to counteract a molecular defect on the so-called “Philadelphia chromosome,” first discovered in 1960. It has since become the standard of care for this disease, and its effectiveness and easily-administered pill form enables most patients to live with CML as a manageable, chronic disease.

Cancer.Net; CML: Treatment Options

N Engl J Med 2001; 344: 1038-42

## 1999

### First targeted anti-breast cancer drug, trastuzumab (Herceptin), has major impact on care

The FDA approves the groundbreaking drug trastuzumab (Herceptin) after research shows that adding the monoclonal antibody to chemotherapy dramatically increases survival for women with advanced breast cancer that over-produces a protein called HER2. In 2006, the drug is also approved as part of adjuvant therapy (after surgery) for women with early-stage HER2-positive breast cancer, after two major trials show that it reduces the risk of recurrence by more than 50 percent, an unprecedented result.

About 25 percent of breast cancer patients have HER2-positive disease, and prior to the introduction of trastuzumab, there were no effective treatments for these cancers, which were considered some of the most aggressive, deadly forms of the disease. Recently, trastuzumab was also FDA-approved to treat patients with stomach cancers that have a similar over-production of the HER2 protein.

Cancer.Net; Breast Cancer: Treatment Options

N Engl J Med 2001; 344: 783-92

N Engl J Med 2005; 353: 1673-84

## 1998

### Chemotherapy before surgery helps more women benefit from breast-conserving treatment

A major trial reports that an approach called neoadjuvant chemotherapy – providing chemotherapy before surgery – allows more than two-thirds of women with large breast tumors to undergo breast-conserving surgery, called lumpectomy, instead of full mastectomy. The goal of neoadjuvant therapy is to shrink tumors so they can be removed surgically. Breast-conserving surgery, also called lumpectomy, is easier to recover from and results in far better cosmetic outcomes – without compromising survival – compared with mastectomy. Neoadjuvant therapy is later shown to benefit patients with rectal and other cancers.

Cancer.Net

Journal of Clinical Oncology 1998; 16(8): 2672-78

Journal of Clinical Oncology 2008; 26(5): 778-85

### Drug therapy can reduce breast cancer risk in women at high risk

The FDA approves tamoxifen (Novaldex), a hormonal drug already used to prevent recurrence of breast cancer, to reduce the risk of developing breast cancer in women who are at high risk for the disease. The approval is based on a large trial showing that tamoxifen reduced breast cancer risk by more than 40 percent in women with a strong family history of breast cancer or with mutations in the BRCA1 and BRCA2 genes. Later research shows that a different drug used to treat osteoporosis, raloxifene (Evista), is as effective as tamoxifen at preventing invasive breast cancer, but with a lower risk of certain side effects.

Cancer.Net; Drugs to Lower Breast Cancer Risk

Journal of the National Cancer Institute 1998; 90(18)

JAMA 2006; 295(23): 2727-41

### New radiotherapy technique enables precise targeting of tumors near sensitive tissue

Doctors begin using intensity modulated radiation therapy (IMRT), a highly advanced radiation technique, to precisely target tumors that lie close to vital organs and other sensitive tissue that must be protected from radiation. IMRT uses sophisticated software and complex new machinery to vary both the shape and intensity of radiation. One of the clearest benefits has been in the treatment of head and neck cancers; IMRT allows doctors to minimize radiation exposure to the spinal cord, optic nerve and salivary glands, reducing side effects without compromising tumor control.

Seminars in Radiation Oncology 1999; 9(1): 60-77

International Journal of Radiation Oncology, Biology, Physics 2001; 50(3): 695–704

## 1997

### Prophylactic surgery helps prevent breast and ovarian cancers in women at high risk

In the mid-1990s, researchers discover that women who have mutations in the genes known as BRCA1 and BRCA2 have a significantly increased risk of developing breast and ovarian cancers. Soon after, studies find that women with the mutations, or with a strong family history of these cancers, may be able to reduce their cancer risk by 90 percent or more by undergoing surgical removal of their breasts (mastectomy), ovaries (oophorectomy), or both. A decade later, a major review of published studies confirms that removal of the ovaries and fallopian tubes in premenopausal women with BRCA mutations reduces the risk of breast cancer by 51 percent and the risk of ovarian and fallopian tube cancers by 79 percent.

N Engl J Med 1999; 340(2): 77-84

N Engl J Med 2002; 346: 1616-22

N Engl J Med 1997; 336: 1401-08

### Surgery found to cure some patients with advanced colon cancer

In general, metastatic cancer is difficult or impossible to treat with surgery because tumor cells are spread throughout the body. But in 1997, researchers find that some colon cancer patients whose cancer has metastasized to the liver only can be cured with surgery. In a study of nearly 300 such patients who underwent surgery between 1960 and 1987, about one in four were still alive five years later, and nearly of all of these patients were found to have been essentially cured. A later study finds that use of positron emission tomography, or PET scanning, can identify some liver metastases that would have gone unnoticed before, helping surgeons in the study to achieve a cure rate above 50 percent.

Archives of Surgery 1997; 132(5): 505-11

Annals of Surgery 2004; 240(3): 438-50

### FDA approves first-ever targeted cancer drug, rituximab

The FDA approves the first molecularly targeted cancer drug, rituximab (Rituxan), to treat patients with B-cell non-Hodgkin lymphoma that no longer responds to other treatments. Rituximab is in a new class of drugs called monoclonal antibodies, and targets a protein on the surface of immune cells known as B cells, interfering with the development of cancer. It is later combined with other cancer therapies to boost cure rates and increase survival.

Journal of Clinical Oncology 1998; 16(8): 2825-33

## 1993

### Taxanes emerge as a vital chemotherapy option for ovarian, breast cancer

A new family of treatments debuts with the FDA approval of paclitaxel (Taxol) for advanced ovarian cancer. The drug receives one of the fastest-ever approvals, on the heels of data showing it shrinks ovarian tumors by more than half in many women who had stopped responding to all other therapies. Later studies show it extends survival by over a year when used as an initial therapy for advanced ovarian cancer, along with the chemotherapy drug cisplatin.

Over the next decade, paclitaxel also proves effective for all stages of breast cancer – extending lives and delaying disease progression compared to existing therapies, and delaying recurrence when used as adjuvant therapy (after surgery). The drug is derived from the bark of a yew tree, and is the product of a field of research exploring ‘natural’ cures for a range of diseases. Until drugmakers discovered a synthetic method for producing the drug, there was widespread concern that the natural resources needed to produce the drug would not meet demand.

Cancer.Net; Treatment Options

Semin Oncol. 1996; 23(5): 40-7

Journal of Clinical Oncology 2003; 21(17): 3194-3200

### Melanoma linked to sun exposure

A growing number of studies indicate that excessive sun exposure, including a history of severe sunburn, increases the risk of melanoma. However, researchers caution that some melanomas can occur in areas of the body without sun exposure, such as on the palms of the hands and soles of the feet. While researchers continue to seek a better understanding of melanoma’s risk factors, a number of leading medical associations have cautioned against excessive sun exposure to reduce the risk of melanoma and other skin cancers.

Cancer.Net; Melanoma: Risk Factors and Prevention

British Journal of Cancer 1982; 46: 955

J Am Acad Dermatol. 1984; 11(1): 674-84

## 1992

### Sentinel lymph node biopsy determines cancer’s spread with fewer side effects

A surgical technique called sentinel lymph node biopsy becomes a less invasive way to assess whether cancer has spread in patients with early-stage melanoma, the most aggressive form of skin cancer. The procedure involves surgically removing the lymph node closest to the primary tumor – the “sentinel” node – and examining it under a microscope for evidence of cancer. If the sentinel node is cancer-free, no further lymph nodes are removed and the patient is spared the previous practice of removing a large number of nodes. This allows for easier recovery and reduces the risk of postoperative side effects such as lymphedema, a painful swelling of the extremities.

Sentinel lymph node biopsy is later found to be effective for women with breast cancer.

Cancer.Net; Sentinel Lymph Node Biopsy for Early-Stage Breast Cancer

JAMA. 1996; 276(22): 1818-22

Journal of Clinical Oncology 2007; 25(24): 3657-3663

## 1991

### Powerful anti-nausea drugs alleviate major side effect of cancer treatment

Ondansetron (Zofran) is approved by the FDA to prevent vomiting caused by chemotherapy and/or radiation. The drug works by deactivating the nervous system’s natural trigger for vomiting. Other, similar drugs are soon approved, including granisetron (Kytril), dolasetron (Anzemet) and palonosetron (Aloxi). These and other anti-nausea drugs, like aprepitant (Emend), make it possible for most cancer patients to receive chemotherapy in an outpatient setting, with minimal disruption to their daily routines.

Cancer.Net; Nausea and Vomiting

N Engl J Med 1990; 322: 810-816

### Cancer deaths begin steady decline

For the first time since record-keeping began in the 1930s, cancer mortality rates begin to decline. The National Cancer Institute, the Centers for Disease Control and Prevention, and the American Cancer Society report that the overall cancer death rate fell by 2.6 percent between 1991 and 1995. Between 1991 and 2008 (the most recent year available), the death rate has fallen by a total of 18 percent.

Cancer 1998; 82(6): 1197-1207

NCI: SEER Cancer Statistics

## 1990

### Shift to 3-D radiation treatment plans increases precision, safety of therapy

Thanks to the integration of powerful computers into medicine, doctors are able to dramatically improve radiation therapy by creating 3-D treatment plans. These plans require highly complex calculations and vastly more computing power than earlier, two-dimensional treatment plans. Thanks to this advance, radiation can be targeted at tumors from multiple angles, with beams of varying power, in ways that minimize the damage to healthy, surrounding tissue.

International Journal of Radiation Oncology 1990; 18(6): 1485-94

### Laparoscopic surgery minimizes pain, recovery time for several cancers

Beginning in the 1990s, laparoscopic surgery – in which a surgeon makes several small incisions and uses telescoping equipment to remove tumors – emerges as an alternative to traditional open surgery for some cancers, including kidney, prostate and colorectal cancer. This new approach allows patients to recover faster and experience less pain, without sacrificing effectiveness.

Cancer.Net; What is Cancer Surgery?

J Laparoendosc Surg. 1993; 3(6): 577-81

N Engl J Med 2004; 350: 2050-59

## 1989

### Drugs to boost blood cells help patients finish cancer treatment, reduce infections

The FDA approves the drug epoetin alpha (Procrit, Epogen) to stimulate production of red blood cells in patients with severe anemia, one of the most common and serious side effects of chemotherapy. These drugs are soon joined by white blood cell-boosting drugs such as filgrastim (Neupogen) and pegfilgrastim (Neulasta). The new treatments help reduce the need for blood transfusions and make chemotherapy safer by reducing the risk of infections and related hospitalizations.

FDA: Information on Erythropoiesis-Stimulating Agents

NCI Fact Sheet: Filgrastim

## 1988

### Benzene discovered to cause blood cancers

Scientists find that occupational exposure to benzene, a chemical commonly used as a solvent and in oil-related products, is associated with increased risk of developing non-lymphocytic leukemia, non-Hodgkin lymphoma, and other diseases. Following this discovery, workers begin taking steps to protect themselves from benzene exposure and reduce their cancer risk.

N Engl J Med 1987; 316: 1044-50

American Journal of Industrial Medicine 1997; 31(3): 287–95

### Adjuvant therapy proven for colorectal cancer

Pivotal clinical trials show that chemotherapy following surgery (adjuvant treatment) in patients with stage III colorectal cancer reduces the risk of cancer recurrence by about 40 percent. Later refinements – using newer drugs, radiation and sophisticated treatment schedules – help to lower recurrence rates even further. Together with greater screening to detect colon cancer early, adjuvant therapy has contributed to a 40 percent reduction in colon cancer mortality in the U.S. since the 1970s.

Cancer.Net; Colorectal Cancer: Treatment Options

NIH Consensus Statement

Cancer 2010; 116(3): 544–73

## 1986

### Global guidelines help ensure proper pain management

Pain is common among patients with advanced cancer but hasn’t always been well-managed. In 1986, the World Health Organization issues clear guidance on the use of pain medications for cancer patients, focusing on stronger, opioid-type drugs such as morphine. The guidelines address widespread concerns about addiction, tolerance and abuse, which made some providers reluctant to prescribe the drugs. Adherence to the guidelines has been found to provide reliable pain relief for up to 90 percent of patients. In later years, other organizations, including ASCO, propose guidelines to help doctors recognize and talk to their patients about pain and its management.

Cancer.Net; Treating Pain with Medication

Annals of Oncology 2005; 16(Supplement 4): iv132 –35

Journal of Clinical Oncology 1992; 10(12): 1976-82

### Tamoxifen reduces breast cancer recurrence

Tamoxifen (Novaldex) is approved as adjuvant therapy for post-menopausal women following breast cancer surgery, based on studies showing that use of the hormonal therapy for five years after surgery reduces the risk of cancer recurrence and dramatically increases survival.

Lancet 1983; 322(8347): 450

Lancet 1998; 351(9114): 1451-67

### Second-hand smoke formally declared a carcinogen

The U.S. Surgeon General, and later the International Agency for Research on Cancer, officially state that second-hand smoke is a carcinogen. A number of cities around the world ban indoor smoking in the years that follow.

Surgeon General Report; Health Consequences of Smoking

Report; WHO & International Agency For Research On Cancer

### PSA test enables early detection of prostate cancer

The FDA approves the first PSA (prostate-specific antigen) test to screen for prostate cancer – the most common form of cancer in men – in men aged 50 and older. In the years that follow, widespread use of PSA testing leads to a significant jump in early-stage prostate cancer diagnoses, sparking debate about whether such screening improves survival or simply leads to diagnosis and unnecessary treatment of slow-growing cancers that would never have become life-threatening.

J Urol. 1992; 147(3): 931-34

## 1982

### Limited surgery helps rectal cancer patients avoid colostomies

A new procedure called total mesorectal excision emerges as a new standard surgical treatment for many patients with rectal cancer. The procedure involves removing only the cancerous region of the rectum, allowing patients to maintain normal bowel function. Previously, nearly all patients with rectal cancer had to undergo permanent colostomies (elimination of waste through an opening in the abdomen connected to a colostomy bag).

Cancer.Net; Colorectal Cancer: Treatment Options

British Journal of Surgery

## 1981

### First cancer vaccine prevents cancer-causing hepatitis B infection

The FDA approves the first vaccine against hepatitis B, one of the primary causes of liver cancer. In 1991, the U.S. begins routine vaccination of all children against hepatitis B, and by 2007, the number of acute hepatitis B cases among children under 15 years declines by 98 percent. Over time, routine vaccination is expected to reduce rates of liver cancer in the U.S. and globally among adults who were vaccinated as children.

CDC; Hepatitis B VIS

J Natl Cancer Inst 2009; 101: 1348–1355

## 1977

### Growing use of mammography saves lives

Regular breast cancer screening with mammography becomes increasingly common, helping to detect cancers at an earlier, more treatable stage. By the mid-1980s, nearly one-third of U.S. women over age 40 are screened. By 2008, the proportion screened approaches 70 percent. High screening rates – and resulting early detection – have contributed to a 27 percent reduction in breast cancer mortality among U.S. women since 1975.

Cancer.Net; Mammography

CDC Report: Health, United States, 2009

### Many women with breast cancer can opt for breast-conserving surgery

Studies show that a procedure called lumpectomy – involving the removal of only the tumor, and not the entire breast – followed by radiation therapy is as effective as mastectomy for women with early-stage breast cancer. The finding helps dramatically reduce the physical and cosmetic side effects of breast cancer treatment and enables women to recover more quickly after surgery and return to their normal lives.

Cancer 1977; 39(6): 2822-26

N Engl J Med 1981; 305: 6-11

### New treatments cure men with testicular cancer

A pivotal trial shows that combining the drugs cisplatin, vinblastine (Velban, Velsar) and bleomycin (Blenoxane) can cure 70 percent of patients with advanced testicular cancer. Cisplatin is approved by the FDA the following year. Today, the overall cure rate for testicular cancer (all stages) is a remarkable 95 percent.

Ann Intern Med. 1977; 87(3): 293-98

## 1975

### First adjuvant chemotherapy increases cure rates for early-stage breast cancer

After overcoming concerns in the cancer community about whether the benefits outweigh the risks, Drs. Bernard Fisher and Gianni Bonadonna demonstrate that chemotherapy after surgery – known as adjuvant chemotherapy – prolongs the lives of women with early stage breast cancer. Their studies involve use of the drugs l-phenylalanine mustard or a combination of cyclophosphamide (Cytoxan), methotrexate and fluorouracil. Adjuvant chemotherapy becomes a major component of treatment for the disease, improving survival and cure rates in the years ahead. Today, about nine in 10 women with early-stage breast cancer are alive five years after their diagnosis.

This finding sets the stage for research on adjuvant therapy in other common cancers, including colon and lung cancer, making it one of the most important advances in modern cancer care.

Cancer.Net; Breast Cancer: Treatment Options

N Engl J Med 1975; 292: 117-122

Annals of the Royal College of Surgeons of England 1981; 63(4): 239–243

### Use of cancer-causing asbestos declines

As studies confirm long-suspected links between asbestos and certain cancers, use of asbestos begins to decline. In the 1980s, its use is banned in a growing number of applications, and environmental and health regulations help to dramatically limit exposure to asbestos in workplaces and homes. Asbestos exposure has been shown to increase a person’s risk of lung cancer, mesothelioma (an aggressive cancer in the chest or abdomen), and other serious health problems. Because these problems often occur decades after exposure, however, the impact of preventive efforts will be felt gradually in the years ahead.

NCI: Asbestos Exposure and Cancer Risk

## 1974

### CT scanning provides clearer images of tumors, guiding radiation and other treatments

Researchers perform the first computed tomography (CT) scan on a human patient – a woman with a suspected brain tumor. CT scanning uses X-rays to create images or “slices” of the brain, allowing doctors for the first time to clearly see tumors arising in the soft tissue of the brain. Over the following decades, CT scanning enables doctors to assess the size, shape and location of many other types of tumors, and to carefully target radiation and surgery to hit the tumors without harming healthy tissue.

X-Ray Computed Tomography in Biomedical Engineering

## 1971

### More limited mastectomy proven effective for early-stage breast cancer

While radical surgery had been routinely used to treat breast cancer, a more limited surgical procedure called total mastectomy (removing just the breast tissue instead of removing the breast, chest wall muscle and underarm lymph nodes) is confirmed to be as effective for women with early-stage breast cancer. The procedure reduces pain after surgery and speeds recovery for patients. This advance paves the way for future breast-conserving surgeries.

Cancer 2006; 28(6)

N Engl J Med 1989; 320: 822-828

Annals of Surgery 1969; 170(6): 880–882

### National Cancer Act of 1971 becomes law

President Richard M. Nixon signs the National Cancer Act in December, less than a year after launching a national “War on Cancer” in his State of the Union address. The act leads to a major expansion of cancer research efforts in the U.S., paving the way for much of the progress achieved over the next 40 years. Among other changes, the Act provides unprecedented levels of funding for the National Cancer Institute ($400 million in 1972 and$600 million by 1974) and directs NCI to expand federal cancer research facilities and award new research grants.

NCI: National Cancer Act of 1937

### Screening tests for colorectal cancer dramatically reduce deaths

In 1967, the guaiac fecal occult blood test (FOBT) is introduced as a screening test for colorectal cancer, one of the most common forms of cancer. This simple and inexpensive tool detects the presence of blood in stool, a sign that cancerous or precancerous growths (called polyps) may be present. Within the next few years, two new screening techniques – flexible sigmoidoscopy and colonoscopy – enable physicians to examine the colon using a small camera attached to a flexible lighted tube. The widespread use of these approaches leads to better detection of precancerous polyps and early stage cancers that are usually curable with surgery. Over the coming decades, routine screening contributes to major reductions in colorectal cancer mortality – a total decline of more than 40 percent since 1975.

Cancer.Net; Colonoscopy

JAMA 1967; 201(12): 943-945

ASCO Guideline

## 1970

### Increased use of radioactive “seeds” to target prostate and other cancers

Studies suggest that an approach called brachytherapy extends the lives of patients with prostate cancer, compared to surgical removal of the prostate and surrounding tissue. In this approach, tiny radioactive sources or “seeds” are implanted directly into the prostate gland, delivering a high dose of radiation directly to the tumor while leaving healthy tissue beyond the prostate relatively unaffected.

Brachytherapy has been used since the early 1900s, but became less common after the widespread adoption of external beam radiation. With refined techniques and conclusive data on its effectiveness, the approach once again becomes a central part of treatment for prostate, cervical and other cancers.

Can J Surg. 1983; 26(4): 363-65

Int J Radiat Oncol Biol Phys. 1991; 21(3): 537-47

## 1965

### Chemotherapy found to cure Hodgkin lymphoma

Researchers led by Vincent DeVita discover that a new chemotherapy regimen called MOPP (mechlorethamine, vincristine, procarbazine and prednisone) cures up to 50 percent of patients with advanced Hodgkin lymphoma. This regimen quickly becomes the standard treatment. In the 1970s, a different chemotherapy combination (doxorubicin, bleomycin, vinblastine and dacarbazine – known as ABVD) proves even more effective, curing about 70 percent of patients with advanced Hodgkin lymphoma. The ABVD combination remains a mainstay of treatment today.

Cancer Research 2008; 68(21): 8643-53

## 1959

### Smoking linked to cancer; cessation campaigns begin

In the 1950s, studies begin to show that smoking is a major cause of cancer, particularly lung cancer. In the early 1960s, both the U.S. Surgeon General and the U.K. Royal College of Physicians issue reports linking smoking to cancer and other serious health problems. In later years, smoking is also established as a major cause of pancreatic cancer, and second-hand smoke is declared a threat to the health of non-smokers. Tobacco control and smoking cessation soon become the most important strategies for reducing the worldwide toll of lung cancer.

British Medical Journal 1950: 84-93

## 1958

### Pioneering “combination chemotherapy” cures leukemia

NCI scientists demonstrate that combination chemotherapy – in which multiple drugs are administered together – can cause remissions in both children and adults with acute leukemia. Their findings set the stage for nearly all modern chemotherapy, in which drug combinations, dosing and scheduling have been carefully refined to maximize effectiveness while minimizing side effects.

Blood 1958; 13:1126-1148

## 1955

### U.S. government establishes national research network to test new cancer treatments

The Clinical Trials Cooperative Group Program is established by the U.S. National Cancer Institute. Over time, this nationwide cancer research network proves the safety and efficacy of many of the most important advances in cancer treatment, screening and prevention. Cooperative Group trials have brought breakthroughs in adjuvant chemotherapy for breast and colon cancers; breast-conserving lumpectomy to avoid mastectomy; and new standards of care for blood cancers, brain tumors, and many others. Perhaps most striking is the impact of these trials on pediatric cancer survival rates. Fifty to 60 percent of children with cancer are enrolled in clinical trials, and childhood cancer survival rates have increased from less than 10 percent in the 1950s to nearly 80 percent today as a result.

IOM Report: A National Cancer Clinical Trials System for the 21st Century

## 1949

### First chemotherapy drug approved for cancer

Following results of clinical trials conducted in 1946 and 1947, nitrogen mustard is approved by the Food and Drug Administration (FDA) for the treatment of Hodgkin lymphoma. Nitrogen mustard – also known as mustard gas and stockpiled as a weapon in World War II – kills cancer cells by modifying their DNA through a process called alkylation. Its discovery spurs rapid advancements in chemotherapy, and the drug still receives some use today in combination chemotherapy for Hodgkin lymphoma.

JAMA. 1946; 132(3): 126-32

British Medical Journal 1970; 4: 259-265

## 1947

### First-ever remission of pediatric leukemia

Sidney Farber, a physician at Children’s Hospital Boston, achieves the first partial remission of pediatric leukemia in a 4-year-old girl using the drug aminopterin. He soon documents 10 cases of remission in a landmark scientific paper. Until this time, children with acute leukemia usually died within weeks of being diagnosed. While early remissions prove temporary, they pave the way for therapies that cure thousands of patients in the decades to come, allowing most childhood cancer patients to live long, healthy lives.

Boston Children’s Hospital

N Engl J Med 1948; 238:787-793

## 1943

### Introduction of Pap test leads to dramatic declines in cervical cancer deaths

The Pap test, named for its inventor, George Papanicolaou, enables doctors to detect and treat cervical cancers or pre-cancers before they have a chance to spread. Since the 1950s, widespread use of the Pap test has helped to reduce U.S. cervical cancer death rates by nearly 70 percent. Yet cervical cancer remains a major cause of cancer death in developing countries, where access to screening and treatment is limited.

Cancer.Net; Pap Test

Yale Journal of Biology and Medicine; Diagnosis of Uterine Cancer by Vaginal Smear

The Journal of Clinical Endocrinology 1945; 5(1): 40-41

## 1937

### National Cancer Institute established

President Franklin D. Roosevelt signs legislation establishing the National Cancer Institute to support research on the causes, diagnosis and treatment of cancer. The new agency’s 1938 budget is \$400,000.

NCI: National Cancer Act of 1937

NCI: 250 Years of Advances Against Cancer

## 1903

### First use of radiation to treat cancer

Five years after Marie Curie’s discovery of radium, doctors report the first successful of use of this radioactive element to treat cancer, in two Russian patients with skin cancer. In the following decades, radiation becomes widely used to treat many different cancers, including cervical, prostate, breast and other tumors. In these first decades, doctors use an approach known as brachytherapy, in which small pieces of radioactive material are implanted inside or next to tumors, delivering radiation to cancer cells at close range. Brachytherapy remains an essential part of cancer treatment today, but has been refined to more precisely target tumor cells while leaving healthy tissue unharmed.

Cancer Journal 2006; 76(10)

American Brachytherapy Society; Introduction of Brachytherapy

NCI: 250 Years of Advances Against Cancer

## 1884

### Radical mastectomy ushers in more aggressive surgical approaches for cancer

Baltimore surgeon William Halsted pioneers a new approach to removing breast tumors, radical mastectomy, in which the entire breast and the surrounding lymph nodes and chest muscles are removed. This helps reduce recurrences of the disease, which was previously nearly always fatal. Halsted’s work also leads to similar approaches for other cancers, in which both the tumor and surrounding tissue are removed. These techniques are still an important part of treatment for some cancers today. For breast cancer, however, surgeries have become far more conservative and effective, enabling many women to avoid mastectomy altogether.