The effect of hormone therapy on breast density following risk-reducing salpingo-oophorectomy in women with an increased risk for breast and ovarian cancer

Barele, Mark van; Buis, C.; Zanten, Monique M.A. Brood-van; Doorn, H Lena C van; Gaarenstroom, Katja N.; Heemskerk-Gerritsen, Bernadette A M; Hooning, Maartje J.; Hullu, Joanne de; Mourits, Marian J.E.; Burger, Curt W.

doi:10.1097/gme.0000000000001844

Cited by 2 publications

(2 citation statements)

References 19 publications

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“…Previous risk-reducing surgeries should therefore be taken into account in the contraceptive advice for BRCA1/2 -PV carriers. In other cases, the use of contraceptives might influence breast cancer management strategies; for example, OCP might increase breast density, as was previously described for hormone replacement therapy, although the data are inconsistent ( van Barele et al , 2021 ; Evans, 2002 ; Lundström et al , 2002 ). Higher breast density negatively affects the evaluability of imaging techniques.…”

Section: Discussionmentioning

confidence: 95%

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis

Bommel¹,

IntHout²,

Veldmate

et al. 2022

Human Reproduction Update

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BACKGROUND Increasing numbers of BReast CAncer (BRCA) 1 or 2 pathogenic variant (PV) carriers, who have an inherited predisposition to breast and ovarian cancer, are being identified. Among these women, data regarding the effects of contraception on cancer risks are unclear and various guidelines provide various recommendations. OBJECTIVE AND RATIONALE We aim to optimize counselling regarding contraception for BRCA1/2-PV carriers. Therefore, we performed a systematic review and meta-analysis. We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used any form of contraception versus non-users. Second, we analysed breast and ovarian cancer risk among BRCA1/2-PV carriers as influenced by the duration of contraceptive use and by the time since last use. In addition, we provide an overview of all relevant international guidelines regarding contraceptive use for BRCA1/2-PV carriers. SEARCH METHODS A systematic search in the Medline database and Cochrane library identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception until June 2021. The search included medical subject headings, keywords and synonyms related to BRCA and contraceptives (any kind). PRISMA guidance was followed. Risk Of Bias In Non-randomized Studies of Interventions and Grading of Recommendations, Assessment, Development and Evaluations assessments were performed. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and for the various contraceptive methods. OUTCOMES Results of the breast cancer risk with oral contraceptive pill (OCP) analysis depended on the outcome measure. Meta-analyses of seven studies with 7525 women revealed a hazard ratio (HR) of 1.55 (95% CI: 1.36–1.76) and of four studies including 9106 women resulted in an odds ratio (OR) of 1.06 (95% CI: 0.90–1.25), heterogeneity (I2) 0% and 52%, respectively. Breast cancer risk was still increased in ever-users compared with never-users >10 years after last OCP use. In contrast, ovarian cancer risk was decreased among OCP users: HR 0.62 (95% CI: 0.52–0.74) based on two studies including 10 981 women (I2: 0%), and OR 0.49 (95% CI: 0.38–0.63) based on eight studies including 10 390 women (I2: 64%). The protective effect vanished after cessation of use. Tubal ligation also protects against ovarian cancer: one study including 3319 women (I2: 0%): HR: 0.44 (95% CI: 0.26–0.74) and three studies with 7691 women (I2: 44%): OR: 0.74 (95% CI: 0.53–1.03). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers. The quality of evidence was either low or very low. WIDER IMPLICATIONS The OCP potentially increases breast cancer risk, while ovarian cancer risk decreases with either the OCP and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers should be personalized; the genetic and non-genetic factors (like prior risk-reducing surgeries, prior breast cancer and age) and patients’ preferences (reversibility, ease of use, reliability and effect on menstrual cycle) should be balanced. To further optimize counselling for high-risk women, future research should focus on other (commonly used) contraceptive methods and cancer risks in this specific population, and on the potential impact of changing formulations over time.

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Section: Discussionmentioning

confidence: 95%

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis

Bommel¹,

IntHout²,

Veldmate

et al. 2022

Human Reproduction Update

View full text Add to dashboard Cite

show abstract

“…In addition, chemoprevention trials have shown that tamoxifen treatment is associated with decreasing breast density [ 33 – 35 ]. Also, surgical removal of both ovaries (bilateral oophorectomy) is associated with decreasing breast density [ 36 , 37 ]. However, there have been very limited studies in which other factors were examined for potential association with longitudinal changes in breast density.…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Longitudinal Changes in Mammographic Density in a Multiethnic Breast Screening Cohort of Postmenopausal Women

Park,

Ziogas,

Feig

et al. 2023

The Breast Journal

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Background. Breast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention. Methods. This study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher’s exact test and multivariate conditional logistic regression. Results. 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density. Conclusions. The associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk.

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The effect of hormone therapy on breast density following risk-reducing salpingo-oophorectomy in women with an increased risk for breast and ovarian cancer

Abstract: The effect of hormone therapy on breast density following risk-reducing salpingooophorectomy in women with an increased risk for breast and ovarian cancer

Cited by 2 publications

References 19 publications

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis

Factors Associated with Longitudinal Changes in Mammographic Density in a Multiethnic Breast Screening Cohort of Postmenopausal Women

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