It’s okay to consider breast-conserving therapy in breast cancer patients with high-risk hereditary genetic mutations, according to guidelines published in the Journal of Clinical Oncology.
The presence of a germline BRCA1 or BRCA2 mutation shouldn’t preclude breast-conserving therapy as long as the patient is otherwise eligible for the procedure, according to the guidelines, which were developed by an expert panel convened by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society for Surgical Oncology.
Nadine M. Tung, MD, of Beth Israel Deaconess Medical Center in Boston and the rest of the expert panel reviewed evidence from 58 published articles to create the guidelines.
In addition to supporting use of breast-conserving therapy, the guidelines suggest that radiation shouldn’t be withheld because of mutation status, except in patients with TP53 mutations. Furthermore, BRCA1/2 mutation carriers with metastatic HER2-negative disease can receive the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib as an “alternative to chemotherapy” for first-, second-, or third-line therapy.
However, it’s the “license to consider breast-conserving therapy” for high-risk individuals that is one of the most noteworthy points in the guidelines, and the one that may surprise some readers, according to William J. Gradishar, MD, of Northwestern University in Chicago, who was not involved in developing the guidelines.
“We don’t have to be as dogmatic with these patients with respect to local therapies as we were in the past,” Dr. Gradishar said in an interview. “That’s a good thing for patients, but you also have to understand the nuances that go into recommending [breast-conserving surgery] to a patient. Other variables, like the age at which the patient develops breast cancer, family history, etc., all go into it.”
Weighing options for surgery
The guidelines emphasize that, for patients with germline BRCA1/2 mutations, health care providers need to discuss treatment options for the breast cancer at hand. However, patients should also be made aware of their increased risk of contralateral and new ipsilateral breast cancer as compared with noncarriers.
When weighing breast-conserving therapy versus mastectomy in light of contralateral breast cancer risk, the guidelines recommend considering not only age at diagnosis – the strongest predictor of a later contralateral breast cancer – but also family history, comorbidities, life expectancy, ability to undergo MRI, and prognosis from breast or other cancers, such as ovarian cancer.
If a bilateral mastectomy isn’t performed in a BRCA1/2 mutation carrier, an annual mammogram and MRI are warranted thereafter for screening of the remaining breast tissue, according to the guidelines.
The guidelines say breast-conserving therapy should be offered to patients with mutations in moderate-penetrance genes, including PALB2, CHEK2, and ATM. However, there’s not much data regarding the risk of ipsilateral breast cancer after breast-conserving therapy in these patients.
Likewise, there’s limited evidence on contralateral breast cancer risk for patients with mutations in moderate-penetrance genes aside from CHEK2. The guidelines say the risk should be discussed with patients “in the context of shared decision making.”
Nipple-sparing mastectomy is “reasonable” to consider in certain newly diagnosed patients with BRCA1/2 mutations, as well as in newly diagnosed patients with moderate-risk mutations, the guidelines state.
Women with breast cancer and a deleterious BRCA1/2 mutation who are undergoing unilateral mastectomy should be offered contralateral risk-reducing mastectomy. Likewise, women with moderate-risk mutations should be offered contralateral risk-reducing mastectomy, but not solely based on mutation status, according to the guidelines. Data are limited on contralateral breast cancer risk related to those mutations.