Diseases / Research

Breast Cancer

Breast carcinoma cells

The stroma of this breast carcinoma is stained brown and the tumor cells are stained in blue.

Photo by Fred Hutch Experimental Histopathology

Click for high-res version

Fred Hutch researchers are reducing breast cancer incidence and death by identifying risk factors for the disease, developing new methods of detecting its presence and helping to predict health outcomes based on a woman’s genetics and other factors. 

Through the Seattle Cancer Consortium Breast SPORE, Hutch researchers are on the forefront of breast cancer research in immunotherapy, tumor microenvironments, cell cycle regulation and genetics that will revolutionize the way we think about and treat patients with breast cancer.

Fast Facts

  • Breast cancer ranks as the most common form of cancer and second-leading cause of cancer death among women in the United States.

  • Breast cancer can occur in any breast tissue, including the cells that produce milk (called lobular carcinoma) and the ducts that carry milk to the nipple (called ductal carcinoma). Although ductal breast cancer is the most common form, researchers have observed that cases of the less-common lobular cancer have been steadily rising.

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Prevention & Causes

Identifying breast cancer risk factors:

Hormone-replacement therapy — The landmark study published in 2002 and conducted by the Women’s Health Initiative (WHI) prompted millions of women to stop taking combined hormone therapy (CHT). In a recent collaboration, WHI investigators and faculty at the Hutchinson Institute for Cancer Outcomes Research (HICOR) created a disease simulation model to evaluate clinical and economic outcomes for CHT-eligible women since the results of the initial study were released. The overall economic return, researchers found, was $37.1 billion over that 10-year period. Furthermore, the simulation showed 126,000 fewer breast cancer cases, 76,000 fewer cases of cardiovascular disease (including coronary heart disease and stroke) and 80,000 fewer cases of venous thromboembolism.  Learn more >

Delayed childbirth and risk — Younger women who wait at least 15 years after their first menstrual period to give birth to their first child may reduce their risk of an aggressive form of breast cancer by up to 60 percent. “We found that the interval between menarche and age at first live birth is inversely associated with the risk of triple-negative breast cancer,” said Dr. Christopher Li, who led the study. Learn more >

Breast cancer survivors and activity levels — Breast cancer survivors could benefit from regular physical activity, yet Dr. Anne McTiernan found few meet the national exercise recommendations during the 10 years after being diagnosed. Prior studies conducted by McTiernan and colleagues show a strong association between physical activity and reduced mortality, extended survival and higher quality of life among breast cancer survivors. Learn more >

Alcohol consumption and breast cancer survival — A study Led by Dr. Polly Newcomb found that drinking before and after diagnosis does not impact survival from the disease. In fact, a modest survival benefit was found in women who were moderate drinkers before and after diagnosis due to a reduced risk of dying from cardiovascular disease, a major cause of mortality among breast cancer survivors. Learn more >

High blood-pressure drugs — A study conducted by Dr. Christopher Li found that women currently taking calcium-channel blockers who have used them for 10 years or longer had an approximately two and a half times higher risk of both invasive ductal and invasive lobular cancers compared to those who never used such calcium-channel blockers and compared to users of other forms of antihypertensives. Learn more >

Vitamin D and weight loss — Chronic inflammation is known to contribute to the development and progression of several diseases, including some cancers. A study led by Dr. Catherine Duggan found that weight loss, in combination with vitamin D supplementation, has a greater effect on reducing chronic inflammation than weight loss alone. Learn more >

Smoking — Young women, current or recent smokers who have smoked a pack a day for a decade or more, have a significantly increased risk of developing the most common type of breast cancer, according to a study by Dr. Christopher Li and colleagues. Learn more >

Fetal cells — Drs. V.K. Gadi and J. Lee Nelson have looked at the role fetal cells play in the development of diseases such as cancer and diabetes. Researchers have long known that pregnancy protects against breast cancer. During microchimerism — a strange-but-true phenomenon where mom’s and baby’s cells mix during pregnancy — there are some beneficial effects. A study led by Gadi found that among women who have had children, those with lower levels of fetal cells in their bloodstream are more likely to develop breast cancer later in life. Learn more >

Sleep and breast cancer survival — A first-of-its-kind study found an association between women who died of breast cancer and poor sleep pre-diagnosis. The study, conducted by Drs. Amanda Phipps and Nathaniel Watson, focused on general lifetime patterns and did not look at sleep patterns after diagnosis. Learn more >

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Detection & Diagnosis

30-year puzzle solved — The gene CTCF, a well-studied DNA binding protein that exerts a major influence on the architecture of the human genome, wasn’t previously linked to cancer. Now, 30 years later, studies conducted by Drs. Gala Filippove and Chris Kemp indicate that loss of one copy of CTCF, a major tumor suppressor gene, caused large-scale epigenetic changes and greatly enhanced the formation of tumors in mice. Learn more >

Tumor dormancyDr. Cyrus Ghajar is investigating ways to prevent breast cancer metastasis by treating dormant disseminated tumor cells. His research is looking at whether controlling the microenvironment around a cell can control the cell. If this microenvironment is disrupted — which can be brought on by inflammation and other processes — the cells will wake up and begin to form tumors. Learn more >

Women’s Health Initiative — Fred Hutch is home of the Clinical Coordinating Center for the Women’s Health Initiative (WHI), which has recruited more than 160,000 post-menopausal women at 40 U.S. research institutions in the mid-1990s to expand medical understanding and improve health care through the study of hormone therapy, diet and nutritional supplement use. WHI discoveries have contributed to better post-menopausal health outcomes, including the first national reduction in breast cancer diagnosis and associated medical costs. The research continues and is expected to find more health and economic benefits. Learn more >

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Treatment & Prognosis

Predicting odds of survival:

Precision cancer treatments — Until recently, the complexities of cancer genomes, the frequent development of drug resistance and the lack of suitable technology have limited the availability and clinical success of targeted therapies. Using high-throughput screening rather than the traditional method of testing one gene at a time, Dr. Christopher Kemp and colleagues Drs. V.K. Gadi, Carla Grandori, Eduardo Mendez and Edward Margolin are working to identify new genes to target that may be highly specific to that patient’s tumor, cutting years off the time required to discover new drug targets. Learn more >

Health outcomes for chemotherapy patients — Underuse of supportive-care drugs known as colony-stimulating factor use can result in serious adverse health outcomes for chemotherapy patients that range from life-threatening infections to interruption of chemotherapy to reduced chemotherapy dose intensity. Hutchinson Institute for Cancer Outcomes Research (HICOR) is leading a clinical trial evaluating the use of colony stimulating factor to reduce the risk of serious infection in patients undergoing chemotherapy for breast, colorectal or lung cancer. The study is a partnership with SWOG, Columbia University and the UW School of Pharmacy, and will investigate whether a health-systems-based intervention can improve adherence to evidence-based guidelines for the use colony-stimulating factor. Learn more >

Improving techniques to identify cancer biomarkers — An international team, led by Fred Hutch researcher Dr. Amanda Paulovich has demonstrated the feasibility of large-scale, standardized protein measurements, which are necessary for validation of disease biomarkers and drug targets. Researchers from three different groups in Seattle, Boston and South Korea were able to reproduce measurements of 319 proteins from human breast cancer cells, showing that the method can be standardized across laboratory and international boundaries. Learn more >
ImmunotherapyDr. Stan Riddell and colleagues are conducting a study using genetic engineering of T cells to target the tyrosine kinase-like orphan receptor ROR1, which is highly expressed at the cell-surface of breast cancers, particularly triple negative breast cancer and can serve as a target for adoptive cell therapy. The Riddell lab designed and optimized ROR1-specific chimeric antigen receptors (CARs) that, when expressed in primary human T cells, have potent antitumor activity in vitro and in pre-clinical tumor models studies against ROR1+ breast cancer cells. Learn more >

Cell cycle-directed therapy — Mutations in genes that regulate cell cycle are among the most common genetic changes in breast cancer cells. Dr. Peggy Porter and colleagues are working to develop cell cycle–directed therapies. Their focus is on new ways to target CDK2 activity to enhance breast cancer therapy, through both p27 modulation, and through abnormal inhibitory phosphorylation. If successful, these approaches may be rapidly translated to new breast cancer treatment strategies. Learn more >

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