Cancer risk and characteristics in older female BRCA1/2 mutation carriers.

Authors

null

Bipin Ghimire

Corewell Health William Beaumont University Hospital, Royal Oak, MI

Bipin Ghimire , Ujjwal Karki , Shiva Shrotriya , Tara Rangarajan , Dana Zakalik

Organizations

Corewell Health William Beaumont University Hospital, Royal Oak, MI, Beaumont Health/Oakland University William Beaumont Medical School, Royal Oak, MI

Research Funding

No funding received
None.

Background: Cancer risk and characteristics in older females with BRCA1/2 mutations are less well studied, and the role of risk-reducing strategies in this population remains unclear. Methods: From a database of 1070 female carriers of BRCA1/2 pathogenic (PV) or likely pathogenic variants (LPV) seen at Nancy and James Grosfeld Cancer Genetics Center in Beaumont Health from January 2006 to December 2021, we identified 283 females who lived to age 65 or older. We analyzed cancer risk and clinical characteristics, focusing on females with cancer diagnosed at age 65 or older. Results: Of the 283 BRCA1/2 carriers, 229 (81%) had a cancer diagnosis, out of which 84 (37%) were diagnosed at age 65 or older. Of all the breast cancer diagnoses (n = 173), 45 (26%) were diagnosed at age 65 or older. Among these 45 patients, median age at diagnosis was 69 years (65-87); majority were BRCA2 carriers (62%), with invasive ductal carcinoma (80%), ER-positive (58%), PR-negative (55%), HER2-negative (97%), high grade (55%) and had stage I or II disease (78%). Fifteen patients (38%) were triple-negative. A minority (32%) received adjuvant chemotherapy, 43% received adjuvant endocrine therapy, and 54% received adjuvant radiation. During a median follow-up of 205 months for all breast cancers (n = 173), there were 52 recurrences, 28 of these (54%) were diagnosed at age 65 or older, of which 13 were contralateral (median time to recurrence: 140 months); 5 were local/regional (median time: 186 months) and 10 were metastatic (median time: 76 months). Ten of the 13 contralateral recurrences (77%) were in BRCA1 carriers. Of the ovarian cancer diagnoses (n = 69), 27 (39%) were diagnosed at age 65 or older. Among these 27 patients, median age at diagnosis was 71 years (65-87); majority were BRCA2 carriers (74%), had serous carcinoma (84%), with stage III or IV disease (96%). Of all ovarian cancers (n = 69), there were 15 recurrences (22%), 9 of them (60%) were diagnosed at age 65 or older. Of the 8 pancreatic cancers, 6 were diagnosed at age 65 or older. Of the 283 BRCA1/2 carriers, 249 still had at least one breast at the time of genetic testing, and 34% elected for risk-reducing mastectomy (RRM). Of the 177 patients with intact ovaries, 71% opted for risk-reducing salpingo-oophorectomy (RRSO). Compared to BRCA carriers with cancer diagnosed under age 65, a smaller proportion of those diagnosed at age 65 or older opted to undergo RRM (26% vs. 40%) or RRSO (67% vs. 78%). Conclusions: Our study reveals that female BRCA1/2 mutation carriers over age 65 continue to retain a significant risk of cancer, including breast, contralateral breast, ovarian, and pancreatic cancer. This finding supports the importance of continued high-risk surveillance and risk-reducing interventions in this growing demographic. Further studies are needed to better define the cancer risks and optimal management of older females with BRCA1/2 mutations.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Prevention, Risk Reduction, and Hereditary Cancer

Track

Prevention, Risk Reduction, and Genetics

Sub Track

Hereditary Cancer Syndromes

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 10610)

DOI

10.1200/JCO.2023.41.16_suppl.10610

Abstract #

10610

Poster Bd #

243

Abstract Disclosures

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