As germline genetic testing becomes more widespread among patients with breast cancer, recommendations for the appropriate management of patients with hereditary breast cancer are needed. Until now, no ASCO guideline has addressed the management of hereditary breast cancer, even for carriers of BRCA1 or BRCA2 mutation. However, new recommendations from a joint guideline expert panel summarize the best available data and expert consensus to help provide a clearer pathway for optimal patient care.1
Sifting Through the Data
The guideline emerged from a recognized need for a more consistent framework to help breast cancer oncologists make local and systemic treatment recommendations. Providers often differ in their management practices for hereditary breast cancer, and there are fewer data available on mutations in the newer breast cancer susceptibility genes (eg, ATM, CHEK2, and PALB2) for oncologists to use to base treatment decisions. Consequently, a joint expert panel was convened with ASCO, the American Society for Radiation Oncology, and the Society of Surgical Oncology to develop such recommendations.
Recommendations were derived from both expert consensus and systematic literature review. Because of the limited high-quality evidence available for the local therapy clinical questions, recommendations were developed using the ASCO-modified Delphi formal consensus methodology.
Dana Zakalik, MD
“This topic is extremely important because genetic testing is being expanded to many women with breast cancer,” said Panel Co-Chair Dana Zakalik, MD, of Beaumont Health, Michigan. “This guideline tries to be knowledge-based and data-driven and calls upon the expertise of those individuals who have a deeper knowledge of genetics in breast cancer. In addition, it performs a valuable service in expanding our practice options for hereditary breast cancer.”
Focus of Recommendations
The recommendations partially focus on the use of breast-conserving therapy and better educating patients about their treatment options and risk profile. “For carriers of BRCA [mutations], women who are eligible for and desire breast-conserving therapy should be offered this as an option. However, discussion about the optimal local therapy choice needs to occur in the context of increased risk of both contralateral and ipsilateral breast cancers after breast-conserving therapy, compared with preventative mastectomies,” said Panel Co-Chair Nadine M. Tung, MD, of Beth Israel Deaconess Medical Center, Boston. “Knowledge regarding the risk of contralateral breast cancer is essential when having these discussions, and risk factors for a second breast cancer, such as age at diagnosis and family history, must be considered.”
Nadine M. Tung, MD
The guideline also notes that breast-conserving therapy should be offered to carriers of mutations in PALB2 or
moderate-risk genes (ie, ATM or CHEK2) who are eligible for this treatment. The panel did recommend annual high-risk screening for these patients.
Furthermore, the panel recommended that for carriers of BRCA mutations with metastatic breast cancer, oncologists should consider a poly (ADP-ribose) polymerase inhibitor (ie, olaparib or talazoparib) vs nonplatinum chemotherapy. Platinum chemotherapy should be considered instead of taxanes for carriers of BRCA1 mutations with metastatic triple-negative breast cancer. However, the routine addition of platinum to standard chemotherapy for carriers of BRCA mutations with early-stage breast cancer is not supported by current data.
“We hope these guidelines give oncologists the guidance to offer breast-conserving therapy, including radiation, to patients with hereditary breast cancer when appropriate,” Dr. Tung said. “Although having preventative mastectomies is the right choice for many carriers of BRCA mutations, it is just one choice to be discussed. Carriers of BRCA mutations diagnosed at a younger age have a higher risk of recurrence, which may influence the choice for prophylactic mastectomies. However, likewise, diagnosis at an older age decreases the risk of a second breast cancer. That knowledge is important to help counsel carriers of BRCA mutations about the right local therapy choice for them.”
Because of the variability in oncologists’ management practices for patients with hereditary breast cancer, one of the main goals of the guideline is to generate more consistent treatment approaches.
“Given so much confusion about the appropriateness and efficacy of breast-conserving therapy and the toxicity of radiation in patients with hereditary breast cancer, the guideline has the potential to impact a substantial number of women with breast cancer,” Dr. Tung said. “That includes the approximately 8% of patients with breast cancer who will be found to have an inherited mutation in one of the breast cancer risk genes.”
Lori Pierce, MD, FASTRO, FASCO
Judy Boughey, MD
“The involvement of radiation, surgical, and medical oncologists in the development of these guidelines was essential,” Dr. Tung continued. Thus, Lori Pierce, MD, FASTRO, FASCO, of the University of Michigan, and Judy Boughey, MD, of Mayo Clinic, Minnesota, served as Radiation and Surgery Oncology Panel Chairs, respectively, and were involved in the guideline development from its inception.
Dr. Zakalik noted there is still some controversy with respect to the management of carriers of BRCA mutation with breast cancer, with many patients being told that a bilateral mastectomy is required. The hope is the guideline will dispel misperceptions that patients do not have a choice and instead reflect what the literature actually states about the consequences of either option—breast-conserving therapy or mastectomy.
“Having observed how this field evolved over the past 15 years, we are in a time of rapidly emerging new data,” Dr. Zakalik said. “There’s a tremendous need to know what to do with this information and how to optimize the care of patients. We hope the knowledge [from this guideline] will lead to better outcomes based on existing evidence and expert consensus.”
DISCLOSURE: For full disclosures of the panel members, visit ascopubs.org.
1. Tung NM, Boughey JC, Pierce LJ, et al: Management of hereditary breast cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology guideline. J Clin Oncol. April 3, 2020 (early release online).
Originally published in ASCO Daily News. © American Society of Clinical
Oncology. ASCO Daily News, April 8, 2020. All rights reserved.