A. Belsare1,2, E. Forester1,3, D. W. Kim4, L. J. Goldstein4, R. J. Bleicher1, M. B. Daly5, A. D. Williams1,5 1Fox Chase Cancer Center, Division Of Breast Surgical Oncology, Department Of Surgical Oncology, Philadelphia, PA, USA 2PhiladelphiaCollege of Osteopathic Medicine, Philadelphia, PENNSYLVANIA, USA 3Rowan University School of Osteopathic Medicine, Stratford, NJ, USA 4Fox Chase Cancer Center, Department Of Hematology/Oncology, Philadelphia, PENNSYLVANIA, USA 5Fox Chase Cancer Center, Department Of Clinical Genetics, Philadelphia, PENNSYLVANIA, USA
Introduction:
Patients with germline pathogenic variants (PVs) in the BRCA genes are not only at high risk for developing breast cancer (BC), but also at higher risk than the general population for developing second BCs. Primary breast cancer (PBC) treatment could impact the histologic subtype of contralateral breast cancer (CBC) or recurrence (RBC), and potentially narrow treatment options, especially if triple-negative (TNBC). The aim of this study is to investigate the impact of PBC treatment on histologic subtype of CBC or RBC in patients with BRCA PVs.
Methods:
We performed a retrospective chart review of patients with BRCA1/2 PVs treated at our institution for BC (1992-2022). Patients with missing histologic characteristics were excluded (except for missing HER2 status prior to 2000). We identified patients who developed CBC or RBC (defined as a second ipsilateral cancer) and compared the histologic subtype to the PBC. We also analyzed the differences in clinicopathologic features between those who did and did not develop CBC or RBC.
Results:
We identified 141 BCs among 120 patients with BRCA1/2 PVs, of whom 21 (18%) developed CBC. CBC was more common among patients with PV in BRCA1 (23%) than BRCA2 (12%). Two patients had synchronous CBC [all four cancers were TNBC], while 19 patients developed metachronous CBC (mCBC) with a mean time of 12.0 ± 8.1 years between PBC and mCBC diagnosis. Complete PBC and mCBC subtypes were known for 11 patients who developed mCBC (Table). All patients except one (whose PBC was HR+/HER2-) had adjuvant chemotherapy, and all HER2+ patients underwent anti-HER2 therapy. A change in subtype between PBC and mCBC was noted in 6 (55%) patients, 5 of whom initially had HER2+ or TNBC, but developed HR+/HER2- mCBC. One patient had HER2+ PBC and developed TNBC mCBC. Considering the 141 breast cancers, 22 (16%) developed RBC (13 locoregional and 9 distant) with a mean time from PBC diagnosis of 9.4 ± 6.6 years. Adjuvant chemotherapy had been administered in 17 (77%) cases. As expected, PBC factors associated with RBC included high grade (78% v. 55%), presence of lymphovascular invasion (43% v. 31%), and more advanced tumor and nodal stage. RBC was less likely among those with HR+/HER2- PBC (25 v. 40%). Complete PBC and RBC subtype were known for 12 patients; only one exhibited a change from TNBC to HER2+
Conclusion:
Treatment of PBC in patients with BRCA1/2 PV does not appear to correlate with narrowed CBC or RBC treatment options (ie. TNBC). Instead, most subtype changes in mCBC were to HR+/HER2-, likely due to older age at diagnosis. While larger data sets are needed, this information may be useful in counseling BRCA patients who are apprehensive of undergoing bilateral mastectomy to treat PBC.
