Investigating the relationship between breast cancer and the postmenopausal period: a systematic meta-analysis

One possible explanation for the ongoing debate surrounding breast cancer risk factors is that differences in assessment methodologies lead to conflicting results. One way to address methodological differences in assessment between studies is to use a single standardized assessment to calibrate cancer studies. To achieve this goal, we conducted a meta-analysis, integrating findings from various studies that utilized menopause risk factors in the evaluation of breast cancer cases. We conducted a systematic literature review from 2010 to 2023 and included studies that examined the association between the postmenopausal period and breast cancer. Among the results, we found statistically significant evidence that the postmenopausal period has a positive association with breast cancer. We identified and carefully reviewed 49 articles considered relevant in the literature review and 12 met all of our inclusion and exclusion criteria. The intercept value was 0.768 (positive), indicating a significant degree of heterogeneity between the studies. The standard error (0.209) suggests that the effect size estimation is more precise and reliable across studies. The observed log odds ratios ranged from −0.1716 to 2.0202, with the majority of estimates being positive (92%). The estimated average log odds ratio based on the random-effects model was 0.7679 (95% Confidence Interval (CI): 0.3590 to 1.1768). Therefore, the average outcome significantly differed from zero (z = 3.6809, p < 0.001). Kendall’s Tau value was 0.455, and the p-value was 0.045, indicating a positive, statistically significant and moderate relationship between breast cancer and the postmenopausal period. The results obtained in this study carry significant implications for shaping public health policies and breast cancer screening programs. Understanding breast cancer cases in the postmenopausal period holds substantial importance in devising tailored treatment strategies. These findings can provide valuable insights for the enhancement of clinical practice, allowing for more effective and individualized treatment approaches.

Postmenopausal period; Breast cancer; Systematic meta-analysis

[1] Rozenberg S, Di Pietrantonio V, Vandromme J, Gilles C. Menopausal hormone therapy and breast cancer risk. Best Practice & Research Clinical Endocrinology & Metabolism. 2021; 35: 101577.

[2] Cabasag CJ, Vignat J, Ferlay J, Arndt V, Lemmens V, Praagman J, et al. The preventability of cancer in Europe: a quantitative assessment of avoidable cancer cases across 17 cancer sites and 38 countries in 2020. European Journal of Cancer. 2022; 177: 15–24.

[3] Chlebowski RT, Anderson GL, Aragaki AK, Manson JE, Stefanick ML, Pan K, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the women’s health initiative randomized clinical trials. JAMA. 2020; 324: 369–380.

[4] Smith T, Sahni S, Thacker HL. Postmenopausal hormone therapy—local and systemic: a pharmacologic perspective. The Journal of Clinical Pharmacology. 2020; 60: S74–S85.

[5] Huang MC, Huang TT, Feng HC, Chen IC, Chang CI, Wang TN, et al. Lifestyle factors and energy intakes with risks of breast cancer among pre-and post-menopausal women in Taiwan. Nutrients. 2023; 15: 3900.

[6] Chlebowski RT, Aragaki AK. The women’s health initiative randomized trials of menopausal hormone therapy and breast cancer: findings in context. Menopause. 2023; 30: 454–461.

[7] Hardy C. Understanding power: bringing about strategic change. British Journal of Management. 1996; 7: S3–S16.

[8] Cochran WG. Some methods for strengthening the common χ2 tests. Biometrics. 1954; 10: 417–451.

[9] The jamovi project. jamovi. (Version 2.4) (Computer Software). 2023. Available at: https://www.jamovi.org (Accessed: 15 August 2023).

[10] R Core Team. R: A Language and environment for statistical computing. (Version 4.1) (Computer software). 2022. Available at: https://cran.r-project.org (Accessed: 18 August 2022).

[11] Viechtbauer W. Conducting meta-analyses in R with the metafor package. Journal of Statistical Software. Link. 2010; 36: 1–48.

[12] Villegas JLV, Choque RAM. Defining a good research question using the PICOT and FINGER format. Gaceta Médica Boliviana. 2020; 43: DEFINING-A.

[13] Xue H, Qiao R, Yan L, Yang S, Liang Y, Liu Y, et al. The correlation between potential “Anti-Cancer” trace elements and the risk of breast cancer: a case-control study in a Chinese population. Frontiers in Oncology. 2021;11: 646534.

[14] Liu L, Zhai W, Wang F, Yu L, Zhou F, Xiang Y, et al. Using machine learning to identify gene interaction networks associated with breast cancer. BMC Cancer. 2022; 22: 1070.

[15] Paleari RG, Peres RM, Florentino JO, Heinrich JK, Bragança WO, del Valle JCT, et al. Reduced prevalence of the C825T polymorphism of the G-protein beta subunit gene in women with breast cancer. The International Journal of Biological Markers. 2011; 26: 234–240.

[16] Campbell Jenkins BW, Addison C, Wilson G, Liu J, Fortune M, Robinson K, et al. Association of the joint effect of menopause and hormone replacement therapy and cancer in African American women: the Jackson heart study. International Journal of Environmental Research and Public Health. 2011; 8: 2491–2504.

[17] Sankar V, Rama P, Mohammed S, John S, Sivakumar V, Rodrigues PA. Association of reproductive risk factors and comorbidities among molecular subtypes of breast cancer in a Tertiary care hospital. Brazilian Journal of Pharmaceutical Sciences. 2022; 58: e18816.

[18] Fatima N, Zaman MU, Fatima T. Increased risk of breast cancer in multiparous and lactating women attending a breast care clinic in Pakistan: a paradigm shift. Asian Pacific Journal of Cancer Prevention. 2010; 11: 1219–1223.

[19] Yang P, Hou M, Ou-Yang F, Tsai E, Wang T. Association of early-onset breast cancer with body mass index, menarche, and menopause in Taiwan. BMC Cancer. 2022; 22: 1–11.

[20] Javed S, Ali M, Sadia S, Aslam MA, Masood AI, Shaikh RS, et al. Combined effect of menopause age and genotype on occurrence of breast cancer risk in Pakistani population. Maturitas. 2011; 69: 377–382.

[21] Oh H, Bodelon C, Palakal M, Chatterjee N, Sherman ME, Linville L, et al. Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue. Breast Cancer Research and Treatment. 2016; 158: 341–350.

[22] Wang X, Li L, Gao J, Liu J, Guo M, Liu L, et al. The association between body size and breast cancer in Han women in northern and Eastern China. The Oncologist. 2016; 21: 1362–1368.

[23] Cho YA, Kim J, Park K, Lim S, Shin A, Sung M, et al. Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status. European Journal of Clinical Nutrition. 2010; 64: 924–932.

[24] Dibaba DT, Braithwaite D, Akinyemiju T. Metabolic syndrome and the risk of breast cancer and subtypes by race, menopause and BMI. Cancers. 2018; 10: 299.

[25] Borenstein M, Cooper H, Hedges L, Valentine J. Effect sizes for continuous data. The Handbook of Research Synthesis and Meta-Analysis. 2009; 2: 221–235.

[26] Key TJ, Balkwill A, Bradbury KE, Reeves GK, Kuan AS, Simpson RF, et al. Foods, macronutrients and breast cancer risk in postmenopausal women: a large UK cohort. International Journal of Epidemiology. 2019; 48: 489–500.

[27] Yaghjyan L, Colditz GA, Rosner B, Tamimi RM. Mammographic breast density and breast cancer risk: interactions of percent density, absolute dense, and non-dense areas with breast cancer risk factors. Breast Cancer Research and Treatment. 2015; 150: 181–189.

[28] Zhu D, Chung H, Dobson AJ, Pandeya N, Giles GG, Bruinsma F, et al. Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data. The Lancet Public Health. 2019; 4: e553–e564.

[29] Rees M, Abernethy K, Bachmann G, Bretz S, Ceausu I, Durmusoglu F, et al. The essential menopause curriculum for healthcare professionals: a European Menopause and Andropause Society (EMAS) position statement. Maturitas. 2022; 158: 70–77.