Breast cancer: more prevention to get higher protection of women’s health

by Antonino Napoleone, Domenico Gangemi, Giuseppe Scarlata | November 1, 2020.

In recent years, research has made great strides, coming to identify pathogenetic mechanisms, as well as innovative therapies that until a few years ago seemed unthinkable. However, sometimes Science needs support, especially when it comes to promoting and trying to implement tools to raise awareness of sensitive issues such as the prevention of certain diseases. It ends this October 2020, a month marked by the sharp increase of Coronavirus (SARS-CoV-2) infections in the world. Yet, this should not distract attention from other important and equally topical issues: October is the month of prevention against breast cancer, it is the month of the pink ribbon to protect the health of women.
Breast cancer is the most frequent and most diagnosed cancer in women, with a growing trend. Even if you have more and more advanced and innovative diagnostic tools and therapies, which have allowed to lengthen the expectations of recovery and life, to date, it is not easy to fully counteract this phenomenon. In this scenario, prevention must be placed before the triad of research-diagnostic-therapy, in order to pursue a common goal in the protection of women’s health.

Epidemiology of breast cancer

In 2012 it was estimated that 1.7 million women were diagnosed with breast cancer and that in the same year about 521,900 women lost their lives. More than two-thirds of breast cancer cases are diagnosed in women aged 50 years or older and most of these cases are found in developed countries. In Italy, 1 woman out of 8 falls ill with breast cancer and it is estimated that every year more than 50,000 cases are diagnosed.
It is less known, but breast cancer also affects men, although in a small percentage (about 1%), where the most representative symptom is the presence of nodules usually below the nipple-areola complex.

Breast anatomy and carcinogenesis

The breast or udder performs important physiological and aesthetic functions in women and consists of glandular, adipose and fibrous tissue (Figure 1). The glandular tissue of the breast is particularly rich in blood vessels, lymphatic vessels and nerve endings and consists of cells that continuously modify and reproduce following the hormonal cycle. Under physiological conditions, this phenomenon is highly regulated and is functional to the maintenance of homeostasis and proper tissue regeneration. However, when the process of carcinogenesis (tumour development) is triggered, these regulatory mechanisms are altered causing the appearance of abnormal cells that grow in an uncontrolled and uncoordinated way compared to the corresponding cells of normal tissue. The process of carcinogenesis is not immediate, but it occurs slowly over several years and certainly, there are several factors called “risk” that affect a lot on the origins of this pathological process.

Risk factors

Several risk factors related to breast cancer have been identified by numerous epidemiological studies and classified into two macro-categories.

Unmodifiable risk factors concern the age, reproductive and genetic history of the woman:

• Age: the likelihood of breast cancer increases with increasing age.
• Reproductive history: early menarche (before the age of 11 years) and late menopause (over 55 years), as well as the absence of pregnancy or first pregnancy over 35 years. It has also been seen that breastfeeding reduces the risk of breast cancer.
• Familiarity: family members with breast and/or ovarian cancer increases by 10% the possibility of getting sick.
• Genetics: mutations in specific genes (BRCA1 and BRCA2) are directly related to the development of breast and ovarian cancer, so it is important to check whether these mutations are inherited from family cases.

Modifiable risk factors concern external environmental factors, as well as habits and lifestyles on which it is possible to act to minimize them:

• Obesity: the risk of breast cancer is higher in women who are overweight and obese.
• Alcohol: the risk increases in proportion to the amount and frequency of alcohol consumption.
• Smoking: the risk of developing breast cancer is higher in smokers.
• Sedentariness: physical activity reduces the risk of contracting breast cancer.
• Hormone Replacement Therapy: taking estrogen and progesterone drugs indicated as replacement therapy after menopause can increase the risk of breast cancer.
• Nutrition: reduced consumption of fruits and vegetables, combined with a diet rich in refined sugars and fats and abuse of red meat especially if grilled or smoked, affects the development of breast cancer.
• External environmental factors: related to prolonged exposure to ionizing radiation or carcinogenic and/or mutagenic substances (i.e. inducing DNA mutations), such as dioxins and vehicle exhaust gases.

Preneoplastic lesions

It is a complex of alterations or lesions that can progress through various stages of maturation over time, in the development of a tumour, and are classified according to their histological or tissue profile. Benign lesions that do not involve an increased risk of breast cancer include adenosis, duct ectasia, simple fibroadenomas, fibrosis, mastitis, mild hyperplasia, cysts and apocrine or squamous metaplasia. Lesions with a slightly increased risk of developing breast cancer are complex fibroadenoma, moderate hyperplasia with or without atypia, sclerosing adenosis and papilloma. Atypical ductal hyperplasia and intraepital lobular neoplasms are the preneoplastic lesions most associated with increased risk of developing breast cancer.

Diagnostics and Screening

Fortunately, thanks to an increasingly accurate, careful and punctual diagnosis, it is possible to effectively identify both preneoplastic lesions and the evolution of tumour tissue, in order to obtain diagnosis at the earliest stages of the disease and as it is easy to imagine, this is a crucial factor in the prognosis of a tumour. In fact, thanks to tests such as Ultrasound Elastosonography, Mammography (3D) with tomosynthesis or contrast medium, Mammary Magnetic Resonance Imaging (MRI) and targeted biopsies under radiological guidance, there are increasingly early diagnosis and reduced mortality, especially in developed countries where these tests have been made more available and accessible.

Breast self-examination

It is important to discover the tumour in its early stages of development, as this greatly increases the possibility of recovery and to intervene without causing any damage or aesthetic injury to the woman. Breast self-exam is a procedure that the woman herself can perform to examine potential suspicious changes that have occurred over time or are persistent (Figure 2). In physiological conditions, the structure of the breast is susceptible to changes in hormone levels, so the self-examination should be performed once a month after the age of twenty, between the seventh and fourteenth day of the menstrual cycle. In menopause, there is no indicated time to perform it. However, it is always advisable to consult a specialist in order to carry out the procedure in the correct way and check for any preneoplastic lesions or other suspicious clinical signs requiring further investigation.

In particular, be careful if:

• The skin of the udder or areola appears altered, reddened, thickened, retracted or with relief nodules.
• The nipple appears retracted, especially if the indentation of the nipple has appeared recently and if small rashes or scabs appear on the skin of the areola.
• Spontaneous secretions from the nipple appear spontaneously, especially if serous or bloody.
• At the palpation of the udder or axillary cavity, it may be noticed the appearance of swelling.
• Redness or changes in shape and size appear in one or both breasts.
  

Therapy and future research perspectives

Research and medicine have certainly made a significant contribution in recent years in the development of increasingly effective and targeted therapeutic options. The range of therapeutic options to date includes surgery, radiotherapy and drug therapies.

Surgery
Surgery is still the most decisive and effective approach for the treatment and complete recovery from breast cancer. Depending on the stage and size of the tumour, limited removal of part of the breast containing the tumour and part of the surrounding healthy tissue (glandular resection, quadrantectomy), or complete removal of the mammary gland together with the nipple, skin and axillary lymph nodes (radical mastectomy) can be performed. The complete removal of axillary lymph nodes is necessary in case of axillary metastases confirmed or evident at the pre-surgical clinical examination. These operations may be followed by plastic surgery to restore the shape and volume of the breast removed in case of mastectomy.

Radiotherapy
Radiation therapy uses high energy ionizing radiation to kill cancer cells and acts in the part of the body where the radiation is administered by an external device. Radiotherapy is also used after surgery to remove any residual tumour cells or to reduce the risk of local recurrences. However, it can cause mainly local side effects, the most common of which are skin irritation, redness, nausea and fatigue.

Pharmacological therapies
Pharmacological therapies aim to eliminate cancer cells and also act on a systemic level on possible metastases, reducing the risk of recurrence and increasing the possibility of recovery. Pharmacological therapies include:

• Chemotherapy
  It provides for the use of anti-tumour drugs that are administered intravenously or orally with the aim of reaching the tumour cells. It is not always necessary, but in some cases, it is highly recommended after surgery (adjuvant chemotherapy) to eliminate possible residual tumour cells, and before surgery (neoadjuvant chemotherapy) in order to reduce the tumour mass. The main side effects are hair loss, vomiting, nausea, lack of appetite, fatigue and also alterations in the menstrual cycle and fertility of the woman.
  
• Hormone or endocrine therapy
  It involves the use of drugs that block the action or production of estrogen and progesterone. It has been demonstrated that these hormones support the growth of tumour cells in patients in which this hormone-cancer cell interaction is detected (hormone-receptor-positive). It is well tolerated with limited side effects and is used either after or before surgery.
  
• Immunotherapy
  This approach involves the use of “biological drugs”, such as monoclonal antibodies, which trigger the patient’s immune system to recognize and kill cancer cells selectively and with reduced side effects. Immunotherapy can be performed through the use of molecules that stimulate and trigger the immune system to recognize and eliminate cancer cells or through the use of molecules that can directly recognize and eliminate cancer cells. The branch of immunoncology is revolutionizing the way to treat tumour diseases, from the early stages to the advanced stages of the disease when metastasis occur, with the hope that in the future it can replace other types of treatment more invasive and aggressive.

Conclusions

In recent years, research has made significant progress and continues to struggle tirelessly to protect women’s health. Breast cancer severely affects a woman’s physical well-being, psychological and aesthetic aspect, during all phases of the disease, even those after the recovery. It is therefore essential to inform and make women aware since prevention is a tool that allows health professionals to act in time, prevent radical treatments and safeguard the health and beauty of women.
ScienceRely supports the pink ribbon campaign for the protection of women’s health.

References

• Razmpoosh, E., Sajadian, A., Vafa, S., Zarrati, M., Raji, M., & Salehi-Abargouei, A. (2020). The effects of lifestyle modification, including dietary and physical activity interventions, on Anthropometric indices and Quality of life of patients with breast cancer: A systematic review and meta-analysis of clinical trials. European Journal of Cancer, 138, S82. https://doi.org/10.1016/S0959-8049(20)30752-8
• Zielonke, N., Gini, A., Jansen, E. E. L., Anttila, A., Segnan, N., Ponti, A., … Priaulx, J. (2020). Evidence for reducing cancer-specific mortality due to screening for breast cancer in Europe: A systematic review. European Journal of Cancer, 127, 191–206. https://doi.org/10.1016/j.ejca.2019.12.010
• Romm, A. (2010). Breast cancer. Botanical Medicine for Women’s Health (First Edition). Elsevier Inc. https://doi.org/10.1016/B978-0-443-07277-2.00012-X
• Kulungowski, A. M., & Finlayson, C. A. (2009). Breast Masses. Abernathy’s Surgical Secrets. Elsevier Inc. https://doi.org/10.1016/B978-0-323-05711-0.00062-8
• Zucca-Matthes, G., Urban, C., & Vallejo, A. (2016). Anatomy of the nipple and breast ducts. Gland Surgery, 5(1), 32–36. https://doi.org/10.3978/j.issn.2227-684X.2015.05.10
• https://www.lilt.it/sites/default/files/allegati/articoli/