Breast Cancer Awareness Month

Published 30.10.2021.

Every October marks a Breast Cancer Awareness Month, an annual remainder for all women (and men with family history of breast cancer) about the importance of early detection of breast cancer and regular diagnostic screening.

According to the global metrics, breast cancer was the most commonly occurring cancer in women in 2020, with 2.3 million diagnosed cases and almost 700 000 breast cancer-associated deaths worldwide. These new cases add to the growing number of 7.8 million women being diagnosed with breast cancer in the last 5 years, which makes breast cancer the most widespread cancer in the world [1]. Furthermore, female breast cancer has now exceeded lung cancer as the most commonly diagnosed cancer, with the latter still being the leading cause of cancer death, followed by breast cancer ranking fifth in cancer mortality worldwide [2]. Latest published data in Croatia reveal that 2845 cases of breast cancer were recorded in 2018 and 722 women died in 2020 [3]. Male breast cancer is rare (<1% of all breast cancers occur in men and <0.5% of deaths in men can be attributed to breast cancer) and often connected to family history [4]. Other risk factors in men include imbalance of estrogen and testosterone, liver cirrhosis, prostate cancer, age, obesity and smoking [5].

Breast cancer occurs when glandular cells start to grow uncontrollably, divide, and destroy surrounding healthy tissue. If malignant, cells can enter blood and/or lymph vessels and spread to other parts of body causing distant metastases. It is molecularly heterogeneous disease [6] whose characteristics involve activation of human epidermal growth factor receptor 2 (HER2), breast cancer (BRCA) gene mutations and activation of hormone estrogen (ER) and progesterone receptors (PR). Clinicians today classify breast cancer in five subtypes according to histological features and expression patterns of pathological markers HER2, ER, PR and Ki67 proliferation marker [7]. Types expressing ER and/or PR are hormone receptor-positive cancers, which respond to therapies leading to good prognosis. On the other hand, breast cancer cells not expressing ER, PR nor HER2 are called triple-negative breast cancer cells and are quite aggressive and unsusceptible to targeted therapies [8].

When treating breast cancer, multidisciplinary approach is used consisting of surgery and radiation as locoregional therapies, and systemic therapy such as hormone treatment (HR-positive cancers), antibody therapies (HER2-positive cancers) and poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers [9]. If caught at the early stage, non-metastatic breast cancer is curable in 70-80% of patients. Contrastingly, advanced form with distant metastases is not curable with existing therapies. It is however treatable in a way that therapies can improve survival and quality of patient’s life.

Propensity to develop breast cancer is dependent on the genetic predisposition, lifestyle, and other environmental factors. Only 10% of breast cancers are hereditary and related to family history [5]. Due to elevated reproductive-associated risk factors (such as advanced age pregnancies, reduced breastfeeding, having fewer children, and usage of contraceptives), along with alcohol consumption, unhealthy diet, physical inactivity and improved mammographic screening, developed countries have much higher incidence rates than developing countries [10]. Even so, incidence is on the rise in developing countries like Africa [11], South America and Asia due to lifestyle changes which bridge gaps between those two groups.

In the case of both developed and developing countries, an effective strategy for improving survival lies in the advancement of early detection, by raising breast cancer awareness, improving breast examination and providing adequate treatments [12,13]. The most used test for an early detection of breast cancer is mammography, an X-ray examination which detects tumors and other changes in the breast that are too small to feel. It can discover changes in the breast about two years earlier than a clinical examination based on the appearance of symptoms or palpable lumps. By self-examination, regular mammography and ultrasound examinations, breast cancer can be detected at an early stage when the chances of cure and survival are much higher. Breast cancer most often occurs over the age of 50, but it can also appear in young women [3]. Women aged 50 to 69 should be mammography-screened every 2 years according to World Health Organization recommendation [14]. It is important to note though, that such screening has limitations which include overtreatment and overdiagnosis [15].

Josip Madunić, PhD, IMROH, Zagreb, Croatia

References
[1] Breast cancer, (n.d.). https://www.who.int/news-room/fact-sheets/detail/breast-cancer (accessed October 25, 2021).
[2] H. Sung, J. Ferlay, R.L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA. Cancer J. Clin. 71 (2021) 209–249. https://doi.org/10.3322/caac.21660.
[3] Listopad – mjesec borbe protiv raka dojke | Hrvatski zavod za javno zdravstvo, (n.d.). https://www.hzjz.hr/sluzba-epidemiologija-prevencija-nezaraznih-bolesti/listopad-mjesec-borbe-protiv-raka-dojke-2/ (accessed October 31, 2021).
[4] Breast Cancer in Men | CDC, (n.d.). https://www.cdc.gov/cancer/breast/men/index.htm (accessed October 25, 2021).
[5] N. Harbeck, F. Penault-Llorca, J. Cortes, M. Gnant, N. Houssami, P. Poortmans, K. Ruddy, J. Tsang, F. Cardoso, Breast cancer, Nat. Rev. Dis. Prim. 2019 51. 5 (2019) 1–31. https://doi.org/10.1038/s41572-019-0111-2.
[6] T. Sørlie, C.M. Perou, R. Tibshiranie, T. Aas, S. Geisler, H. Johnsen, T. Hastie, M.B. Eisen, M. van de Rijn, S.S. Jeffrey, T. Thorsen, H. Quist, J.C. Matese, P.O. Brown, D. Botstein, P.E. Lønning, AL. Børresen-Dale, Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications, Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 10869–10874. https://doi.org/10.1073/PNAS.191367098
[7] C. Lundgren, P.-O. Bendahl, Å. Borg, A. Ehinger, C. Hegardt, C. Larsson, N. Loman, M. Malmberg, H. Olofsson, L.H. Saal, T. Sjöblom, H. Lindman, M. Klintman, J. Häkkinen, J. Vallon-Christersson, M. Fernö, L. Rydén, M. Ekholm, Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer, Breast Cancer Res. Treat. 178 (2019) 459. https://doi.org/10.1007/S10549-019-05378-7.
[8] J. Madunić, The Urokinase Plasminogen Activator System in Human Cancers: An Overview of Its Prognostic and Predictive Role, Thromb. Haemost. 118 (2018) 2020–2036. https://doi.org/10.1055/s-0038-1675399.
[9] E. Heer, A. Harper, N. Escandor, H. Sung, V. McCormack, M.M. Fidler-Benaoudia, Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study, Lancet Glob. Heal. 8 (2020) e1027–e1037. https://doi.org/10.1016/S2214-109X(20)30215-1.
[10] F.Z. Francies, R. Hull, R. Khanyile, Z. Dlamini, Breast cancer in low-middle income countries: abnormality in splicing and lack of targeted treatment options, Am J Cancer Res. 10 (2020) 1568–1591. www.ajcr.us/ (accessed October 26, 2021).
[11] W.Y. Joko-Fru, E. Jedy-Agba, A. Korir, O. Ogunbiyi, C.P. Dzamalala, E. Chokunonga, H. Wabinga, S. Manraj, A. Finesse, N. Somdyala, B. Liu, P. McGale, A. Jemal, F. Bray, D.M. Parkin, The evolving epidemic of breast cancer in sub-Saharan Africa: Results from the African Cancer Registry Network, Int. J. Cancer. 147 (2020) 2131–2141. https://doi.org/10.1002/IJC.33014.
[12] T.T. Ngan, N.T.Q. Nguyen, H. Van Minh, M. Donnelly, C. O’Neill, Effectiveness of clinical breast examination as a ‘stand-alone’ screening modality: an overview of systematic reviews, BMC Cancer 2020 201. 20 (2020) 1–10. https://doi.org/10.1186/S12885-020-07521-W.
[13] J.K. Birnbaum, C. Duggan, B.O. Anderson, R. Etzioni, Early detection and treatment strategies for breast cancer in low-income and upper middle-income countries: a modelling study, Lancet. Glob. Heal. 6 (2018) e885–e893. https://doi.org/10.1016/S2214-109X(18)30257-2.
[14] WHO Position Paper on Mammography Screening – NCBI Bookshelf, n.d. https://www.ncbi.nlm.nih.gov/books/NBK269545/ (accessed October 30, 2021).
[15] D. Puliti, S.W. Duffy, G. Miccinesi, H. de Koning, E. Lynge, M. Zappa, E. Paci, Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review, J. Med. Screen. 19 Suppl 1 (2012) 42–56. https://doi.org/10.1258/JMS.2012.012082.