Abstract P1-09-03: Impact of BRCA1/2 pathogenic variants on ipsilateral breast tumor recurrence and prognosis following breast-conserving surgery

Abstract

Background The risk of ipsilateral breast tumor recurrence (IBTR) and the prognostic outcome of breast-conserving surgery (BCS) for germline BRCA1/2 pathogenic variant (BRCA1/2+) carriers remain controversial. We examined differences in IBTR and prognosis between BRCA1/2+ carriers and non-carriers following BCS for breast cancer. Methods Clinical and pathological data were collected by retrospectively reviewing charts of consecutive patients with stage 0-III breast cancer who underwent genetic testing for germline BRCA1/2 and BCS between 1996 and 2020. Patients with variants of breast cancer-associated genes other than BRCA1/2 were excluded. We compared the incidence of IBTR and prognosis, including overall survival (OS), breast cancer-specific survival (BCSS), and distant recurrence-free survival (DRFS), between BRCA1/2+ carriers and non-carriers. Results We analyzed 551 patients (587 breasts with cancer), including 30 BRCA1+ carriers (32 breasts) and 31 BRCA2+ carriers (32 breasts). The median follow-up was 5.8 years (7.2 and 5.3 years for carriers and non-carriers, respectively). The median age at breast cancer diagnosis was 43 and 46 years for carriers and non-carriers, respectively, indicating younger onset of cancer in carriers (age ≤ 40 years; 46.9% for carriers vs. 27.5% for non-carriers, p = 0.001). In carriers, breast cancer more frequently expressed estrogen receptor-negative (56.2% for BRCA1+ carriers and 15.6% for BRCA2+ carriers vs. 22.0% for non-carriers, p = 0.013), progesterone receptor-negative (62.5% for BRCA1+ carriers and 31.3% for BRCA2+ carriers vs. 29.5%, p = 0.005), nuclear grade III (45.3% for carriers vs. 29.5% for non-carriers, p = 0.010), or a higher Ki-67 index (Ki-67 index > 20) (89.5% vs. 61.8%, p = 0.001) than non-carriers. Moreover, carriers underwent chemotherapy more frequently than non-carriers (62.5% vs. 42.4%, p = 0.002). Cancer stage, tumor size, HER2 status, presence of lymphovascular invasion, and the rate of positive or close surgical margins did not statistically differ between the examined groups. No statistical differences were detected in the number of patients who underwent whole-breast radiotherapy following BCS: 59 breasts in carriers and 503 in non-carriers (92.2% vs. 96.4%). During follow-up, we noted that 9 breasts of BRCA1/2+ carriers (5 [15.6%] for BRCA1+ and 4 [12.5%] for BRCA2+) and 35 breasts (6.7%) of non-carriers developed IBTR (p = 0.035). In an analysis excluding patients who did not undergo radiotherapy, the rate of IBTR remained significantly higher in BRCA1/2+ carriers (p = 0.034) than that in non-carriers. The median time to IBTR was 10.2 years in carriers (10.2 years for BRCA1+ and 8.5 years for BRCA2+) and 3.5 years in non-carriers. Carriers were more likely than non-carriers to exhibit distinct subtypes of recurrent tumors in the ipsilateral breast (66.7% for carriers vs. 19.4% for non-carriers, p = 0.006), occurring in a different quadrant from the primary tumor (50.0% vs. 27.3%, p = 0.215). No significant differences in OS (p = 0.068), BCSS (p = 0.109), or DRFS (p = 0.359) were noted between carriers and non-carriers. Conclusion BRCA1/2+ carriers exhibited a higher risk of IBTR after BCS and a longer time to IBTR than non-carriers. One limitation of the present study is a longer follow-up period for carriers than for non-carriers, as carriers typically underwent long-term observation at our institution; hence, further data accumulation is warranted for validating these findings. Subtypes and quadrants of IBTR were frequently distinct in carriers, indicating the increased incidence of new primary breast cancer. Although the prognosis did not differ between carriers and non-carriers, our results suggest the necessity for long-term intensive breast surveillance of BRCA1/2+ carriers after BCS. Citation Format: Sakiko Kondo, Kumiko Kida, Misato Suzuki, Chika Fukano, Atsushi Yoshida, Naoki Hayashi, Junko Takei, Michiko Yamanaka, Hideko Yamauchi. Impact of BRCA1/2 pathogenic variants on ipsilateral breast tumor recurrence and prognosis following breast-conserving surgery [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-03.