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. 2019 Apr 18;21(1):52.
doi: 10.1186/s13058-019-1135-y.

Regular Use of Aspirin and Other Non-Steroidal Anti-Inflammatory Drugs and Breast Cancer Risk for Women at Familial or Genetic Risk: A Cohort Study

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Free PMC article

Regular Use of Aspirin and Other Non-Steroidal Anti-Inflammatory Drugs and Breast Cancer Risk for Women at Familial or Genetic Risk: A Cohort Study

Rebecca D Kehm et al. Breast Cancer Res. .
Free PMC article

Abstract

Background: The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced breast cancer risk, but it is not known if this association extends to women at familial or genetic risk. We examined the association between regular NSAID use and breast cancer risk using a large cohort of women selected for breast cancer family history, including 1054 BRCA1 or BRCA2 mutation carriers.

Methods: We analyzed a prospective cohort (N = 5606) and a larger combined, retrospective and prospective, cohort (N = 8233) of women who were aged 18 to 79 years, enrolled before June 30, 2011, with follow-up questionnaire data on medication history. The prospective cohort was further restricted to women without breast cancer when medication history was asked by questionnaire. Women were recruited from seven study centers in the United States, Canada, and Australia. Associations were estimated using multivariable Cox proportional hazards regression models adjusted for demographics, lifestyle factors, family history, and other medication use. Women were classified as regular or non-regular users of aspirin, COX-2 inhibitors, ibuprofen and other NSAIDs, and acetaminophen (control) based on self-report at follow-up of ever using the medication for at least twice a week for ≥1 month prior to breast cancer diagnosis. The main outcome was incident invasive breast cancer, based on self- or relative-report (81% confirmed pathologically).

Results: From fully adjusted analyses, regular aspirin use was associated with a 39% and 37% reduced risk of breast cancer in the prospective (HR = 0.61; 95% CI = 0.33-1.14) and combined cohorts (HR = 0.63; 95% CI = 0.57-0.71), respectively. Regular use of COX-2 inhibitors was associated with a 61% and 71% reduced risk of breast cancer (prospective HR = 0.39; 95% CI = 0.15-0.97; combined HR = 0.29; 95% CI = 0.23-0.38). Other NSAIDs and acetaminophen were not associated with breast cancer risk in either cohort. Associations were not modified by familial risk, and consistent patterns were found by BRCA1 and BRCA2 carrier status, estrogen receptor status, and attained age.

Conclusion: Regular use of aspirin and COX-2 inhibitors might reduce breast cancer risk for women at familial or genetic risk.

Keywords: Breast cancer; Family history; High-risk population; Non-steroidal anti-inflammatory drugs.

Conflict of interest statement

Ethics approval and consent to participate

All participants in the BCFR and kConFab provided written informed consent before participation. Human research ethics committees at the participating institutions granted ethics approval for the six sites of the BCFR and for kConFab:

Northern California—Cancer Prevention Institute of California, Institutional Review Board (2001–033) and Stanford University School of Medicine, Institutional Review Board (45842).

New York—Columbia University Medical Center, Institutional Review Board (AAA7794).

Philadelphia—Fox Chase Cancer Center, Institutional Review Board (95–009).

Utah—Huntsman Cancer Institute, University of Utah, Institutional Review Board (00004965).

Ontario—Mount Sinai Hospital Research Ethics Board (#02–0076-U) and University Health Network Research Ethics Board (#96-U107-CE).

Australia—University of Melbourne, Human Ethics Sub-Committee (1441420.1).

kConFab—Peter MacCallum Cancer Centre, the Peter Mac Ethics Committee (97/27).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Overview of the timeline of events in the Prospective Family Study Cohort. Legend: BCFR, Breast Cancer Family Registry; kConFab, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. The prospective cohort includes women who were enrolled before June 30, 2011, aged 18–79 years at follow-up, with data on regular NSAID use, and with no personal history of breast cancer when regular NSAID use was asked by follow-up questionnaire (N = 5606). The combined cohort includes all women enrolled before June 30, 2011, aged 18–79 years at baseline, with data on regular NSAID use asked by follow-up questionnaire. In both cohorts, women were censored at the earliest of the following events: risk-reducing bilateral mastectomy, age 80 years, loss to follow-up, or death
Fig. 2
Fig. 2
Adjusted hazard ratios and 95% confidence intervals of breast cancer risk comparing regular users of aspirin and COX-2 inhibitors with non-regular users by subgroups from analysis of the combined cohort of the Prospective Family Study Cohort (N = 8233). Legend: Models are adjusted for race/ethnicity, study center, baseline age, familial risk profile, cigarette smoking, alcohol consumption, hormone therapy use, hormonal birth control use, and regular use of other medications; stratified by birth cohort. Sample sizes: non-carriers (includes true negatives and women who did not undergo genetic testing) N = 6395; BRCA1 mutation carriers N = 506; BRCA2 mutation carriers N = 418; ER status: N = 7319; attained age 45: N = 2222; attained age 55: N = 4401; attained age 65: N = 6325. Alternative ER subtypes were censored at diagnosis (e.g., ER negative and ER status missing breast cancers censored at age at diagnosis in the analysis of ER positive breast cancer). P values are for the Wald chi-square test statistic for the interaction between categories of familial risk profile or BRCA carrier status and regular medication use
Fig. 3
Fig. 3
Adjusted hazard ratios and 95% confidence intervals of breast cancer risk comparing regular users of ibuprofen and other NSAIDs and acetaminophen with non-regular users by subgroup in the combined cohort of the Breast Cancer Prospective Family Study Cohort (N = 8233). Legend: Models are adjusted for race/ethnicity, study center, baseline age, familial risk profile, cigarette smoking, alcohol consumption, hormone therapy use, hormonal birth control use, and regular use of other medications; stratified by birth cohort. Sample sizes: non-carriers (includes true negatives and women who did not undergo genetic testing) N = 6395; BRCA1 mutation carriers N = 506; BRCA2 mutation carriers N = 418; ER status: N = 7319; attained age 45: N = 2222; attained age 55: N = 4401; attained age 65: N = 6325. Alternative ER subtypes were censored at diagnosis (e.g., ER negative and ER status missing breast cancers censored at age at diagnosis in the analysis of ER-positive breast cancer). P values are for the Wald chi-square test statistic for the interaction between categories of familial risk profile or BRCA carrier status and regular medication use
Fig. 4
Fig. 4
Cumulative risk of breast cancer by regular aspirin use and underlying familial risk. Legend: Predicted age-specific cumulative risk (from birth) for breast cancer, by regular aspirin use and familial risk, where 12% lifetime risk is approximately the population risk of breast cancer by age 80 years, where moderate familial risk (> 20–30% full lifetime BOADICEA) is equivalent to having one affected first-degree relative, and high familial risk (> 30% full lifetime BOADICEA) is equivalent to having two affected first-degree relatives

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