Cancer Res Treat.  2024 Jan;56(1):143-148. 10.4143/crt.2023.653.

Short-term Impact of Hormone Replacement Therapy on Risk of Breast Cancer in BRCA Mutation Carriers: A Nationwide Study in South Korea

• Kim HY
• Park J
• Moon SJ
• Jeong S
• Hong JH
• Lee JK
• Cho GJ
• Cho HW

• KMID: 2550331
• DOI: http://doi.org/10.4143/crt.2023.653

Abstract

Purpose
BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO.
Materials and Methods
A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups.
Results
There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278).
Conclusion
In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO.

Keyword

Breast neoplasms; Female; Genes; Germ-line mutation; Hormone replacement therapy; Mutation; Menopause; Salpingo-oophorectomy

Figure

• 

  Fig. 1. Flow chart of the study. HIRA, Health Insurance Review & Assessment Service; RRSO, risk-reducing salpingo-oophorectomy.

• 

  Fig. 2. Breast cancer incidence among BRCA mutation carriers by hormone replacement therapy (HRT) use. (A) Breast cancer incidence among BRCA mutation carriers who used any HRT compared with women who did not use HRT. (B) Breast cancer incidence among BRCA mutation carriers under the age of 45, who used any HRT compared with women who did not use HRT. (C) Breast cancer incidence among BRCA mutation carriers over the age of 45 who used any HRT compared with women who did not use HRT.

Reference

References

1. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994; 266:66–71.

2. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994; 343:692–5.

3. Daly MB, Pilarski R, Berry M, Buys SS, Farmer M, Friedman S, et al. NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017. J Natl Compr Canc Netw. 2017; 15:9–20.

4. Gallicchio L, Whiteman MK, Tomic D, Miller KP, Langenberg P, Flaws JA. Type of menopause, patterns of hormone therapy use, and hot flashes. Fertil Steril. 2006; 85:1432–40.

5. Madalinska JB, Hollenstein J, Bleiker E, van Beurden M, Valdimarsdottir HB, Massuger LF, et al. Quality-of-life effects of prophylactic salpingo-oophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. J Clin Oncol. 2005; 23:6890–8.

6. Finch A, Metcalfe KA, Chiang JK, Elit L, McLaughlin J, Springate C, et al. The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation. Gynecol Oncol. 2011; 121:163–8.

7. Lobo RA. Surgical menopause and cardiovascular risks. Menopause. 2007; 14:562–6.

8. Yoshida T, Takahashi K, Yamatani H, Takata K, Kurachi H. Impact of surgical menopause on lipid and bone metabolism. Climacteric. 2011; 14:445–52.

9. Michaelson-Cohen R, Gabizon-Peretz S, Armon S, SrebnikMoshe N, Mor P, Tomer A, et al. Breast cancer risk and hormone replacement therapy among BRCA carriers after riskreducing salpingo-oophorectomy. Eur J Cancer. 2021; 148:95–102.

10. Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2005; 23:7804–10.

11. Kotsopoulos J, Gronwald J, Karlan BY, Huzarski T, Tung N, Moller P, et al. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncol. 2018; 4:1059–65.

12. Kim H, Choi DH. Distribution of BRCA1 and BRCA2 mutations in Asian patients with breast cancer. J Breast Cancer. 2013; 16:357–65.

13. Kurian AW. BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol. 2010; 22:72–8.

14. Haffty BG, Choi DH, Goyal S, Silber A, Ranieri K, Matloff E, et al. Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups. Ann Oncol. 2009; 20:1653–9.

15. Li CI, Malone KE, Daling JR. Differences in breast cancer hormone receptor status and histology by race and ethnicity among women 50 years of age and older. Cancer Epidemiol Biomarkers Prev. 2002; 11:601–7.

16. Kim HA, Kim S, Seo YI, Choi HJ, Seong SC, Song YW, et al. The epidemiology of total knee replacement in South Korea: national registry data. Rheumatology (Oxford). 2008; 47:88–91.

17. Eisen A, Lubinski J, Gronwald J, Moller P, Lynch HT, Klijn J, et al. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst. 2008; 100:1361–7.

18. Kotsopoulos J, Huzarski T, Gronwald J, Moller P, Lynch HT, Neuhausen SL, et al. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study. Breast Cancer Res Treat. 2016; 155:365–73.

19. Finch AP, Lubinski J, Møller P, Singer CF, Karlan B, Senter L, et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2014; 32:1547–53.

20. Terra L, Beekman MJ, Engelhardt EG, Heemskerk-Gerritsen BA, van Beurden M, Roeters van Lennep JE, et al. Sexual functioning more than 15 years after premenopausal risk-reducing salpingo-oophorectomy. Am J Obstet Gynecol. 2023; 228:440.

21. Stan DL, Shuster LT, Wick MJ, Swanson CL, Pruthi S, Bakkum-Gamez JN. Challenging and complex decisions in the management of the BRCA mutation carrier. J Womens Health (Larchmt). 2013; 22:825–34.

22. Gordhandas S, Norquist BM, Pennington KP, Yung RL, Laya MB, Swisher EM. Hormone replacement therapy after risk reducing salpingo-oophorectomy in patients with BRCA1 or BRCA2 mutations; a systematic review of risks and benefits. Gynecol Oncol. 2019; 153:192–200.