Molecular and physiological facts affected breast cancer development

1Alyaa Saad Abed, 2Ismaeel Saad Abed Karkosh, 3Zahraa Saad Abed Karkosh

1Applied Biotechnology Department/ College of Biotechnology/ Al-Qasim Green University/ Babylon 51013, Iraq.

2Faculty of Pharmacy -University of Kufa.

3Ibn Sina University of medical and pharmaceutical sciences,Iraq, Baghdad.

*Corresponding Author.: saadaliaa85@yaahoo.com

Abstract

Breast cancer (BC) is the second most common cancer in the world and the most prevalent malignancy in Iraqi women. Radiotherapy has traditionally been one of the most prevalent cancer treatments (RT). Many attempts have been undertaken in recent years to increase dose distribution uniformity to a specified target volume while giving a minimal dosage to surrounding organs at risk. On the other hand, Individual patients may respond to RT in quite diverse ways. The individual variation reflects the fundamental processes that control radiation damage response, which is dictated by various cellular events governed by a large number of genes and their interactions.Many attempts have been undertaken in recent years to increase dose distribution uniformity to a specified target volume while giving a minimal dosage to surrounding organs at risk. On the other hand, Individual patients may respond to RT in quite diverse ways.It have been surveyed papers related to BC in order to distinguish the main molecular and physiological causes.

Keywords: Molecular survey, Physiological survey, Breast cancer.

Introduction

Breast cancer is the second most common cancer in the world and the most prevalent malignancy in Iraqi women. Radiotherapy has traditionally been one of the most prevalent cancer treatments (RT). Many attempts have been undertaken in recent years to increase dose distribution uniformity to a specified target volume while giving a minimal dosage to surrounding organs at risk. On the other hand, Individual patients may respond to RT in quite diverse ways. The individual variation reflects the fundamental processes that control radiation damage response, which is dictated by various cellular events governed by a large number of genes and their interactions ( Baneen Mahmood Habeeb, et. al., 2022).

According to GLOBOCAN 2020, female breast cancer has now overtaken lung cancer as the most prevalent malignant tumor globally, with an estimated 2.26 million new cases annually(Sung, H. et al.2020).

This alarming statistic highlights the urgent need for effective treatment strategies. Recent advancements in imaging screening(Pace, L. E. & Keating, N. L., 2014), surgical techniques(Magnoni, F. et al., 2021), radiotherapy(Castaneda, S. A. & Strasser, 2017), and therapeutic drugs have markedly improved the prognosis for breast cancer patients. Nonetheless, the complexity and heterogeneity of breast cancer necessitate personalized treatment approaches (Yeo, S. K. & Guan, J. L., 2017).

The development of microarray and next-generation sequencing technologies has enabled polygenic testing, providing clinicians with additional clinical insights (Lewis and Vassos, , 2020).

The significance of polygenic testing in breast cancer management has grown considerably, ranging from PAM50 for molecular typing, to the 21-gene (Oncotype DX Breast Recurrence ScoreR) )Cognetti and Naso, ,2021) and MammaPrint™ 70-gene signature (Slodkowska, and Ross, 2009), both of which are crucial in assessing clinical risk and informing treatment decisions in breast cancer cases.

The causes of breast cancer are not fully known. Cancer is a dangerous disease but breast cancer in women is a most serious problem in not even present time in future in worldwide (Dumitrescu and Shields, 2005).

Cancer is metastasis which is a complex series of steps in which cancer cells migrate from one organ (original tumor site) to another organ of the body through the circulatory and lymphatic system. Breast cancer is fundamentally a systemic disease. Estrogens are closely related to the pathogenesis of breast cancer. Breast cancer is the most commonly occurring neoplastic disease in women worldwide and is second only to lung cancer as a cause of cancer death in women. There is a gradual increase in breast cancer incidence in most developed countries and in societies that became westernized recently or are in the process. Breast cancer is the second most common cancer among Indian women (Mukherjee S, et. al., 2006).

The main aim of this review article is to compile a various reason for breast cancers that can be avoidable. Breast cancer is the most frequently diagnosed cancer in women, the incidence rate of which has increased considerably among women in recent years. The established risk factors include (a) menstrual and reproductive history, (b) family history of breast cancer, (c) Postmenopausal obesity, (d) genetic susceptibility (e) Tobacco smoking, and (f) exposure to ionizing radiation. Yet more than half of breast cancer risk remained unexplained (Shivpoojan Kori, 2018).

Figure 1: Breast anatomy(Shivpoojan Kori, 2018).

In Figure 1, Breast anatomy: Each breast contains 15 to 20 lobes of glandular tissue, arranged like the petals of a daisy. The lobes are further divided into smaller lobules that produce milk for breast-feeding. Small tubes (ducts) conduct the milk to a reservoir that lies just beneath your nipple (Shivpoojan Kori, 2018).

Some Popular Causes and risk factors of Breast Cancer

Environmental factors: slightly more control women reported one or more environmental factors as risks for breast cancer. However specific chemicals were rarely identified by participants, who generally referred to broad factors such as ‘pollutants’, ‘toxins’ or ‘additives’ in describing environmental risks. A number of chemicals found in the environment, such as benzene (found in vehicle exhausts), are known carcinogens although with no definite connection to breast cancer. Some pesticides have been shown to mimic the effects of estrogen and it is plausible that they could increase breast cancer risk, although the current epidemiological evidence is weak (Thomson AK, et. al., 2014).

Alcohol use: Drinking alcohol is a one of the most important factor to cause breast cancer (Thomson AK, et. al., 2014).

Alcohol promotes the level of estrogen and other hormones associated with hormones, receptors which are responsible to cause breast cancer . It also may enlarge breast cancer risk by DNA damage in cells. Compare to teetotaler women, women who have thrice alcoholic drinks per week have a 15% higher risk of breast cancer(Shivpoojan Kori, 2018).

Tobacco use: Smoking increases the risk of many: types of cancer (including cancers of the lung, kidney and pancreas). Although findings on a possible link to breast cancer remain mixed, there’s growing evidence smoking may slightly increase the risk of breast cancer. More research is needed before solid conclusions can be made about a potential link between smoking and breast cancer. Some studies have shown smoking before a first childbirth may increase the risk of breast cancer. Others have found no link between the two. Tobacco smoking may be one of the few modifiable risk factors for breast cancer(Shivpoojan Kori, 2018).

Genetic risk factors: The attribution of breast cancer development to inherited or genetic factors was the most commonly identified cause among control women, a finding previously re- ported by others. About 5% to 10% of breast cancer cases are thought to be hereditary, caused by gene changes (mutations) inherited from a parent. Inherited mutations in BRCA1 or BRCA2 are the most common cause of hereditary breast cancer. Women with BRCA mutations have a high risk of developing breast cancer during their lifetime. When they do develop it, they are often younger than other women with breast cancer who are not born with one of these gene mutations. Mutations in other genes are less common causes of inherited breast cancer (Sanderson et. al. ,2009; Shivpoojan Kori, 2018).

DNA changes: Most likely cause to changes in the genetic material (DNA) in our cells. DNA changes are often related to our lifestyle, but some can be due to age and other factors. Cancer is intimately related to the accumulation of DNA damage, and repair failures (including mutation prone repair and hyperactive repair systems). Davis et al. has discussed the overlap between classification schemes of breast cancers and the relationship between DNA damage and breast cancer and endogenous-exogenous sources of DNA damage, and how DNA damage might accumulate in a woman’s breast tissue over her lifetime. They have elaborates the role of molecular biology of three important DNA damage response genes, BRCA1 (Breast cancer 1), BRIT1 [BRCT-repeat inhibitor of hTERT expression], a repressor of human telomerase function, is implicated in cellular immortalization. and PARP-1 (Poly [ADP-ribose] polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1 is an enzyme that in humans is encoded by the PARP1 gene) (Davis and Lin , 2011).

Changes or mutations in DNA can cause normal breast cells to become cancer. Certain DNA changes are passed on from parents (inherited) and can greatly increase your risk for breast cancer. Acquired DNA changes take place over time and are only in the breast cancer cells.
Certain inherited DNA mutations (changes) can dramatically increase the risk
for developing certain cancers and are linked to many of the cancers that run in some families (Scully et. al., 2012).

Aging: Breast cancer risk increases as a woman gets older. As the population ages, an increasing fraction of women diagnosed with breast cancer will be elderly. Heterogeneity of breast cancer risk factors between pre- and postmenopausal women is recognized, but few studies have examined elderly women specifically. The authors describe the age-specific influence of risk factors for postmenopausal breast cancer, with emphasis on women aged 75 or more years (Shivpoojan Kori, 2018).

Family history of breast cancer: Women who have a close blood relative with this disease have a higher risk for breast cancer (Shivpoojan Kori, 2018).

Menstrual cycles: Breast cancer risk increases with earlier menstruation and later menopause.86 For example, breast cancer risk is about 20% higher among those who begin menstruating before age 11 compared to those who begin at age 14 or older. Likewise, women who experience menopause at age 55 or older have about a 12% higher risk compared to those who do so between ages 50-54 (Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol. 2012;13(11):1141-1151.).

Endogenous hormone levels: Postmenopausal women with naturally high levels of certain endogenous sex hormones (e.g., estrogen, progesterone) have about twice the risk of developing breast cancer compared to women with the lowest levels, with the strongest relationships found for HR+ tumors(Sampson JN, et al. 2017; Brown SB, Hankinson SE., 2015)

Breastfeeding: Most studies suggest that breastfeeding for a year or more slightly reduces a woman’s overall risk of breast cancer, with longer duration associated with greater risk reduction. In a review of 47 studies in 30 countries, the risk of breast cancer was reduced by 4% for every 12 months of breastfeeding (Breast Cancer Facts & Figures 2019-2020. American Cancer Society. Breast Cancer Facts & Figures 2019-2020. Atlanta: American Cancer Society, Inc. 2019).

The protective effect may be stronger for – or even limited to – triple negative cancers (Faupel-Badger et al. , 2013; Islami et. al. , 2015;Ma et al., 2017).

Physical inactivity: Women who get regular physical activity have a 10%-20% lower risk of breast cancer compared to women who are inactive, with greater risk reduction associated with increasing levels of activity.( McTiernan A, et al., 2019; Kerr J, Anderson C, Lippman SM. Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. (Moore et al., 2016; Pizot et al., 2016).

Conclusions

Probabilities of developing or dying from breast cancer were calculated using DevCan 6.7.7 (Probability of Developing Cancer Software), developed by the National Cancer Institute (DevCan: Probability of Developing or Dying of Cancer Software, Version 6.7.7; Statistical Research and Applications Branch, National Cancer Institute, April 2019. Available from surveillance.cancer.gov/devcan).

These probabilities reflect the average experience of women in the US who were not previously diagnosed with breast cancer and do not take into account individual behaviors and risk factors (e.g., utilization of mammography screening and family history of breast cancer) (Breast Cancer Facts & Figures 2019-2020. American Cancer Society. Breast Cancer Facts & Figures 2019-2020. Atlanta: American Cancer Society, Inc. 2019).

Acknowledgment

This work was financially supported by many studies of respected scientists, so highly acknowledged and highly thankful to all these researchers.

Conflicts of Interest

Non.

References

Baneen Mahmood Habeeb, Anfal Ali Shakir, Alyaa Saad Abed, (2022). The Role of ATM gene in Iraqi Breast Cancer Patients Undergoing Radiotherapy. ISSN: 0005- 2523 Volume 62, Issue 06, August, 2022.
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.
Pace, L. E., & Keating, N. L. (2014). A systematic assessment of benefits and risks to guide breast cancer screening decisions. Jama, 311(13), 1327-1335.
Magnoni, F., Alessandrini, S., Alberti, L., Polizzi, A., Rotili, A., Veronesi, P., & Corso, G. (2021). Breast cancer surgery: new issues. Current Oncology, 28(5), 4053-4066.
Castaneda, S. A., & Strasser, J. (2017). Updates in the treatment of breast cancer with radiotherapy. Surgical Oncology Clinics, 26(3), 371-382.
Yeo, S. K., & Guan, J. L. (2017). Breast cancer: multiple subtypes within a tumor?. Trends in cancer, 3(11), 753-760.
Lewis, C. M., & Vassos, E. (2020). Polygenic risk scores: from research tools to clinical instruments. Genome medicine, 12(1), 44.
Cognetti, F., & Naso, G. (2021). The clinician’s perspective on the 21-gene assay in early breast cancer. Oncotarget, 12(26), 2514.
Slodkowska, E. A., & Ross, J. S. (2009). MammaPrint™ 70-gene signature: another milestone in personalized medical care for breast cancer patients. Expert review of molecular diagnostics, 9(5), 417-422.
Dumitrescu RG, Shields PG (2005) The etiology of alcohol-induced breast cancer. In Alcohol 35(3):213-225.
Mukherjee S, Koner BC, Ray S, Ray A (2006) Environmental contaminants in pathogenesis of breast cancer. Indian J Exp Biol 44(8): 597-617.
Shivpoojan Kori, (2018). An Overview: Several Causes of Breast Cancer. Epidemiology international journal. Volume 2 Issue 1 Received Date: June 15, 2018 Published Date: July 18, 2018.
Thomson, A. K., Heyworth, J. S., Girschik, J., Slevin, T., Saunders, C., & Fritschi,L. (2014). Beliefs and perceptions about the causes of breast cancer: a case-control study. BMC research notes, 7, 1-8.
Sanderson SC, Waller J, Jarvis MJ, Humphries SE, Wardle J (2009) Awareness of lifestyle risk factors for cancer and heart disease among adults in the UK. Patient Educ Couns 74(2): 221-227.
Davis JD, Lin SY (2011) DNA damage and breast cancer. World J Clin Oncol 2(9): 329-338.
Scully OJ, Bay BH, Yip G, Yu Y (2012) Breast Cancer Metastasis. Cancer Genomics and Proteomics 9: 311-320.
Collaborative Group on Hormonal Factors in Breast Cancer. (2012). Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. The lancet oncology, 13(11), 1141-1151.
Sampson, J. N., Falk, R. T., Schairer, C., Moore, S. C., Fuhrman, B. J., Dallal, C. M., … & Gierach, G. L. (2017). Association of estrogen metabolism with breast cancer risk in different cohorts of postmenopausal women. Cancer research, 77(4), 918-925.
Brown, S. B., & Hankinson, S. E. (2015). Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Steroids, 99, 8-10.
Islami, F., Guerra, C. E., Minihan, A., Yabroff, K. R., Fedewa, S. A., Sloan, K., … & Jemal, A. (2022). American Cancer Society’s report on the status of cancer disparities in the United States, 2021. CA: a cancer journal for clinicians, 72(2), 112-143.
Faupel-Badger, J. M., Arcaro, K. F., Balkam, J. J., Eliassen, A. H., Hassiotou, F., Lebrilla, C. B., … & Sherman, M. E. (2013). Postpartum remodeling, lactation, and breast cancer risk: summary of a National Cancer Institute–sponsored workshop. Journal of the National Cancer Institute, 105(3), 166-174.
Ma, H., Ursin, G., Xu, X., Lee, E., Togawa, K., Duan, L., … & Bernstein, L. (2017). Reproductive factors and the risk of triple-negative breast cancer in white women and African-American women: a pooled analysis. Breast Cancer Research, 19, 1- 14.
Islami, F., Liu, Y., Jemal, A., Zhou, J., Weiderpass, E., Colditz, G., … & Weiss,
M. (2015). Breastfeeding and breast cancer risk by receptor status—a systematic review and meta-analysis. Annals of Oncology, 26(12), 2398-2407.
McTiernan, A. N. N. E., Friedenreich, C. M., Katzmarzyk, P. T., Powell, K. E., Macko, R., Buchner, D., … & Piercy, K. L. (2019). Physical activity in cancer prevention and survival: a systematic review. Medicine and science in sports and exercise, 51(6), 1252.
Kerr, J., Anderson, C., & Lippman, S. M. (2017). Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. The Lancet Oncology, 18(8), e457-e471.
Moore, S. C., Lee, I. M., Weiderpass, E., Campbell, P. T., Sampson, J. N., Kitahara,C. M., … & Patel, A. V. (2016). Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA internal medicine, 176(6), 816-825
Pizot, C., Boniol, M., Mullie, P., Koechlin, A., Boniol, M., Boyle, P., & Autier,
P. (2016). Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies. European journal of cancer, 52, 138-154.
Feuer, E. J., & Wun, L. M. (1999). DEVCAN: probability of developing or dying of cancer. Software, version, 4.