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Etiology, Biology and Treatment of Breast Cancer

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Introduction

Breast cancer is the next most common cancer detected among women in the United States after skin cancer, at a rate of 1 in 3 cancers in women. It is the next leading cause of cancer death among women after lung cancer (DeSantis et al. 2014). Women who are less than the age of 40 account for 6.6% of all breast cancer cases, 2.4% in women less than 35years and 0.65% in women less than 30years (Assi et al. 2013).

This and many trends found in data suggest that older age is a risk factor. Overall, the burden of breast cancer has increased between 1975 and 2000, and this is thought to be attributable to the increasing life expectancy and widespread influence of American and European culture lifestyle with all its risk factors. Death rates of breast cancer have been steadily decreasing, especially in younger women, due to improvements in earlier detection and better treatment options.

Even though the diagnosis of breast cancer is less common among women younger than 40, it could present more aggressively in comparison to its presentation in the older population. This is because it tends to present at a later stage when the disease has advanced and the prognosis is poorer. Many studies attribute this to an aggressive biological subtype of the disease or because of a low index of detection due to the anatomy of the breast at younger ages that would lead to a delay in diagnosis. In 2015, around 231,840 new cases of invasive breast cancer and 40,290 deaths due to breast cancer are expected among women in the United States.

In addition, about 60,290 new cases of in situ breast cancer are expected (DeSantis et al. 2016). According to Breast Cancer.org, 1 in 8 women (12.4%) will acquire invasive breast cancer over the course of her lifetime. In 2018, around 266,120 cases of invasive breast cancer and 63,960 cases of non-invasive breast cancer are predicted to be diagnosed in women. Amongst men, 2,550 new cases of invasive breast cancer are predicted as a man’s lifetime risk of breast cancer is 1 in 1000.

The rates of breast cancer incidence and mortality vary amongst women in age and ethnicity. The average age for female breast cancer diagnosis is 61years. The median age is younger in black women at 58years compared to white women at 62years. The median age of death is 68years overall, with 69years for white women and 62years for black women. (DeSantis et al. 2016). Non-Hispanic white and non-Hispanic black women have the highest rates of cancer incidence and death in comparison to women in other ethnicities. Asian Pacific Islander women have the lowest recorded incidence and death rates due to breast cancer. Even though the overall incidence of breast cancer is lower in black women compared to white women, the death rate is 42% higher in blacks. Based on these statistics breast cancer is an imperative issue amongst women and men with a growing incidence rate.

Etiology of Breast Cancer

As many different types of cancers, the exact cause of breast cancer is unknown, however, there are multiple risk factors and genetic factors that have been shown to have a strong association. For instance, the difference in mortality and incidence rate among women of different ethnicities were attributed to different biological and non-biological factors and lifestyles. Lower breast cancer rates in American Indian or Alaska Native women, Hispanic and Asian Pacific Islander are due to the variation in breast cancer risk factors.

For instance, Hispanic women tend to have a larger number of children and American Indian or Alaska Native women have their first child and a younger age in comparison to women of other ethnic groups and race; these have been found to be protective against breast cancer. Additionally, Asian Pacific Islander women are more likely to breastfeed their children for a minimum of 12 months, less probable to drink alcohol and have lower rates of obesity, which are all protective factors against breast cancer (DeSantis et al. 2016).

Other risk factors include an earlier menarche, a later age at menopause, however, induced menopause is suggested to be a protective factor compared to the naturally occurring one. When it comes to pregnancy, despite the woman’s age, it impacts a short-term increase in the risk of breast cancer due to the surge of estrogen during this time, followed by a long-term reduction of risk. The earlier the age of the first pregnancy, the longer the subsequent long-term protection against developing breast cancer. In premenopausal women, prolonged lactation conveys at most modest protection. There is a small increase in risk with current or recent use of oral contraceptives and long-term use of replacement estrogen with progestin.

High birth weight has been linked to an increase in risk of breast cancer in the offspring. A high-density mammogram (75% or more of the total breast area with dense mammographic appearance) has been associated with a more than 4-fold risk in comparison to a low-density mammogram (10% or less or total breast area with dense mammographic appearance). Atypical (abnormal-looking cells) hyperplasia (overgrowth of cells) of the mammary gland has been documented as an important breast cancer risk factor. A family history among first-degree relatives is a positive risk factor. A personal history of breast cancer exponentially increases your risk of recurrence.

Genetic factors such as BRCA1 and BRCA2, as well as some other highly penetrant mutations, account for a small proportion of breast cancer cases, as most cases are from sporadic mutations. High levels of physical activity and intake of vegetables and fruits have been shown to decrease the risk of acquiring breast cancer, perhaps due to the reduction of endogenous estrogen levels. There is no conclusive or significant association between smoking and breast cancer. Ionizing radiation is a well-known cause of cancer of the breast as well as of several other cancers.

Women who took a medication called diethylstilbestrol (DES), which was used to prevent miscarriages from the 1940s to the 1960s have a slight increase in the risk of developing breast cancer. The women whose mothers took DES are at an even higher risk of developing breast cancer in the future (Trichopoulos et al. 2008). Lastly being overweight in women after menopause is associated with an increased risk of breast cancer because fat tissue is the body’s main source of estrogen then the ovaries stop producing them. Therefore, having more fat tissue is equivalent to higher levels of estrogen in the body, which has been associated with breast cancer.

Biology of Breast Cancer

Like many other cancers, breast cancer is an uncontrolled growth of abnormal breast cells. This growth could occur as a result of abnormal changes or mutation in the genes that are responsible for regulating the growth of the cell. This abnormality could begin in the lobules, which are milk-producing glands, or in the ducts, which is the passage of the milk to the nipples from the lobules.

Over time these cancerous cells can invade nearby healthy breast tissue and even travel to other parts of the body through lymph nodes and the lymphatic system. The lymphatic system drains excess fluid from the body in the form of lymph therefore it travels to all parts of the body just are arteries and veins. The extent of the spread of the cancerous cells determines the stage of breast cancer and therefore the treatments that would be available.

There are various types of breast cancer invasive breast cancer and breast cancer in situ. The difference is in the name, invasive breast cancer is cancer that has invaded the basement membrane and spread to neighboring healthy cells, while cancer in situ is confined within the basement membrane but continues to grow. There is no evidence that cancer in situ could later turn in to invasive breast cancer.

There are various types of breast cancer namely Invasive ductal carcinoma (IDC), Invasive lobular carcinoma (ILC), Ductal carcinoma in situ, Inflammatory breast cancer, lobular carcinoma in situ, Phyllodes tumor of the breast, Paget’s disease of the nipple, Molecular subtypes of breast cancer and Metastatic breast cancer. IDC is further broken down into subtypes, tubular, medullary, mucinous, papillary and cribriform (Li et al. 2005).

Approaches to Breast Cancer Prevention and Control

The most imperative method of prevention is knowledge of the disease to evaluate one’s risks to make dietary or lifestyle changes and as needed visits to a family doctor to be physically evaluated. A patient history is very important as it could give so much information about the patient in terms of their history of breast cancer and lifestyle, which would then tailor the appropriate screening methods.

For instance, in women whose mothers had breast cancer at a younger age, screening would start ten years before that age or at the age of 50, whichever comes first. Secondly, the Physical examination is extremely important as it could detect any changes in the breast anatomy that are associated with breast cancer. Changes such as masses, asymmetries, skin changes like edema, nipple retraction or inversion and skin inflammation or swelling.

Based on various clinical based researches, the US Preventative Service Task Force recommends biennial screening mammography for women between the ages of 50 to 74 years old. The recommendations were based on the risk reduction, the number of women needed to invite for screening to prevent one breast cancer death, and potential for harm from additional testing and biopsies. The sensitivity of mammography is limited by breast density and 10 to 15% of clinically evident breast cancer has no associated abnormality on imaging. Other forms of imaging and screening are available.

Ultrasonography- this is useful in determining whether a breast lesion that has been detected on mammography is solid or cystic. In which case, a cystic mass could be aspirated and the fluid further tested, while a solid mass could be biopsied for further pathologic testing.

Magnetic Resonance Imaging (MRI)- this is increasingly being used to evaluate breast abnormality. It is useful in detecting a primary tumor with axillary lymph node metastasis with no mammographic image evidence. The sensitivity of the MRI is greater in detecting invasive cancer as opposed to detecting cancer in situ.

In order to determine the level of malignancy of breast imaging to access options of treatment, there is a category that is followed to grade breast imaging. This is called Breast Imaging Reporting and Data System (BI-RADS) (Townsend et al. 2017).

Category Definition

  1. Incomplete assessment- needs additional imaging evaluation or prior mammograms for comparison.
  2. Negative- nothing to comment on; usually recommend annual screening.
  3. Benign finding- usually recommends annual screening.
  4. Probably benign finding (4 Suspicious abnormality (2-95% malignant)- biopsy should be considered.
  5. Highly suggestive of malignancy (>95% malignant)- appropriate action should be taken.
  6. Known biopsy-proven malignancy.

These forms of screening and detection of breast cancer have been very successful as it provides a chance of early detection and intervention. The overall death rates of breast cancer have also decreased in the past few decades due to improvements in treatment options such are mastectomies, radiation, and chemotherapy.

Proposed Solution

Advances in breast cancer disease treatment are towards less invasive modes of treatment. More treatment options include lumpectomy (removal of a portion of the breast) as oppose to mastectomy (removal of all of the breast). Currently, there are various researches and trials to improve chemotherapy and radiation treatment options and screening modalities. Other forms of prophylaxis medication such as tamoxifen for women with increased risk of breast cancer (atypical hyperplasia of the breast) have also been seen to be recently beneficial in reducing the risk of breast cancer. Overall breast cancer is a broad and growing field in medicine, there is still a lot unknown and room for advancement.

References

  1. DeSantis, C., Ma, J., Bryan, L., and Jemal, A. (2014). Breast Cancer Statistics, 2013. Ca Cancer J Clin;64:52–62. Doi: 10.3322/caac.21203.
  2. DeSantis, C., Fedewa, S., Sauer, A., Kramer, J., Smith, R., and Jemal, A. (2016). Breast Cancer Statistics, 2015: Convergence of Incidence Rates Between Black and White Women. Ca Cancer J Clin ;66:31–42. Doi: 10.3322/caac.21320
  3. Assi, H., Khoury, k., Dbouk, H., Khalil, L., Mouhieddine, T., and El Saghir. N. (2013). Epidemiology and prognosis of breast cancer in young women. J Thorac Dis 5(S1):S2-S8. Doi: 10.3978/j.issn.2072-1439.2013.05.24
  4. Trichopoulos, D., Adami, H., Ekbom, A., Hsieh, C., and Lagiou, P. (2008). Early life events and conditions and breast cancer risk: From epidemiology to etiology. Int. J. Cancer, (122), 481–485. Doi: 10.1002/ijc.23303
  5. Breast Cancer.Org: US Breast Cancer Statistics. Last modified- October 16, 2018.Retrieived from: https://www.breastcancer.org/symptoms/understand_bc/statistics
  6. Li, C., Uribe, D., and Daling, J. (2005). Clinical characteristics of different histologic types of breast cancer. British Journal of Cancer. (93), 1046 – 1052
  7. Gallager, S. (1984). Pathologic Types of Breast Cancer: Their Prognoses. Cancer ,(53) 623-629.
  8. Townsend, C., Evers M., Beauchamp, D and Mattox K. (2017). Sabiston Textbook of Surgery: The biological basis of Modern Surgical Practice 20th Edition. Chapter 34, Section VII.

Cite this paper

Etiology, Biology and Treatment of Breast Cancer. (2021, Mar 18). Retrieved from https://samploon.com/etiology-and-biology-of-breast-cancer/

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