Reassessing Mandatory Mastectomy Recommendations

By Cari Wade Gervin
Monday, July 20, 2020

New guidelines on how to treat hereditary breast cancer could be a gamechanger.

In early April, the American Society of Clinical Oncology, American Society for Radiation Oncology and the Society of Surgical Oncology released the first-ever guidelines on how best to manage patients with hereditary breast cancer, from the perspective of both local and systemic management.

According to Nadine M. Tung, MD, the study’s lead author, the new guidelines could result in less women with BRCA1 and BRCA2 mutations having preventative double mastectomies. Dr. Tung has worked in oncology for 30 years and studied genetic testing for the past 20 years.

“Prior to these guidelines, I would often hear that patients with BRCA mutations must have bilateral mastectomies,” says Dr. Tung, who is an associate professor at Harvard Medical School and the Director of the Cancer Risk and Prevention Program at Beth Israel Deaconess Medical Center. “For a 60-year-old mutation carrier with her first breast cancer, I think that a woman has a choice and should be informed of her risk of a second contralateral breast cancer in order to help her make the most evidence-based choice and the one that is right for her.”

The full guidelines, published in the Journal of Clinical Oncology, include detailed recommendations for a multitude of clinical questions and explain the research assessed for each. However, it was limited to the five most common genes for which inherited mutations are associated with breast cancer: BRCA1, BRCA2, PALB2, CHEK2 and ATM.

The guidelines include tables that assess the risk for BRCA mutation carriers based on age at diagnosis. Other factors that should be weighed include a woman’s ability to get an annual breast MRI, her prognosis, other comorbidities and her ability to receive chemotherapy.

“With annual breast MRI and mammogram surveillance, for those women who choose to keep their breasts, early detection of future breast cancer is quite feasible,” Dr. Tung says. “Making this difficult decision starts by understanding what a woman’s risk of a second breast cancer is.”

Although many patients will still need bilateral mastectomy based on the above factors or because it decreases the risk of subsequent breast cancer, Dr. Tung says their research found insufficient data that there is an overall survival benefit for BRCA1 or BRCA2 mutation carriers who receive the procedure.

“Thus, the committee concluded that breast-conserving therapy should be offered as an option if appropriate and desired,” Dr. Tung says.

The guidelines also recommend that breast cancer patients with the more moderate-risk mutations CHEK2 or ATM should not have bilateral mastectomies solely due to the mutation. Dr. Tung says that patients with an ATM mutation have regularly been told they should have a mastectomy because radiation is not an option, but the new guidelines recommend the option of breast conservation.

“There has been a lot of controversy regarding whether radiation therapy increases local toxicity or CBC in women who have inherited a single ATM mutation,” Dr. Tung says. “After reviewing the existing data, the committee feels that radiation should be offered to these patients. We concluded that there are insufficient data to withhold it.”

Other key takeaways from the guidelines include:

  • Patients with metastatic HER2-neg breast cancer who have a germline BRCA mutation should be offered a PARP inhibitor instead of non-platinum chemotherapy.
  • Platinum chemotherapy should not added to chemotherapy regimens for BRCA mutation carriers early in treatment because it introduces additional toxicity without proven efficacy.
  • Platinum chemotherapy is preferable to a taxane agent for BRCA mutation carriers with metastatic breast cancer.
  • For women with BRCA1 or BRCA2 who are having mastectomies, nipple-sparing mastectomy is a reasonable approach if medically appropriate.
  • Patients with inherited P53 mutations should have a mastectomy and in most cases not receive radiation.

Although the guidelines are generally for the treatment of women with breast cancer, Dr. Tung cautions that men who have a family medical history of BRCA1 or BRCA2 mutations should undergo genetic counseling to consider testing.

“Men with BRCA2 mutations develop a particularly aggressive type of prostate cancer that has lower survival,” Dr. Tung says. “Men with BRCA2 mutations should undergo prostate cancer surveillance and act on any abnormalities immediately.”

Dr. Tung hopes the guidelines can be updated in future years with additional information as more is known about other mutations.

“This is very exciting,” Dr. Tung says. “Genetic testing not only helps us to stratify risk for future cancers, and implement risk-based screening and prevention strategies, it now helps us choose the most effective cancer treatment.”

Non-Oncology Drugs Found to Kill Cancer Cells

A study from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute found that almost 50 drugs in a database of 4,518 FDA-approved or drugs otherwise proven safe can kill cancer cells while leaving other cells intact. The study, published in January in the journal Nature Cancer, is the largest of its kind and was applied to 578 cancer cell lines.

According to a press release from the Broad Institute, the study’s lead scientists did not have high hopes that drugs approved to treat ailments as varied as alcoholism, diabetes, high cholesterol and arthritis (in dogs) could be useful for treating different types of cancers, and they were pleasantly surprised. Many of the drugs appear to kill cancer cells by activating a protein or stabilizing a protein-protein interaction instead of blocking a protein, as most current cancer drugs do.

While more research is needed, the study shows promise for possible cancer treatments using drugs that are already available, saving millions of dollars in the drug development process.