What is Breast Cancer?
Breast cancer is the cancer of breasts that happens due to genetic mutations. This type of cancer can develop either in the lobules or the ducts of the breast or in the fatty tissue or the fibrous connective tissue of the breast. According to the Breast Cancer Research Foundation (BCRF), breast cancer is the most common cancer amongst women worldwide with over 2 million cases diagnosed annually.
Breast is the second most common cancer overall, and it is the most frequently diagnosed cancer in women of 140 out of 184 countries. According to the American Cancer Society (ACS), 276,480 new cases of breast cancer in women will be diagnosed in the United States in 2020 alone with an estimated female death rate of 42,170.
Breast cancer is a common oncological pathology with an overall 5-year survival rate of 99% for localized disease, 85% for regional disease, and 27% for distant-stage disease. It is more common in developed countries rather than developing and more common in women than men.
What are the different types of breast cancer?
Breast cancer has many types that fall under the two main categories; breast cancer in situ and invasive breast cancer. In situ cancer usually is non-invasive and stays in place, never invading the surrounding areas whereas invasive cancer may spread from the glands to the other parts of the breast. The most common types of breast cancer are mentioned below:
- Ductal carcinoma in situ
- Invasive ductal carcinoma
- Lobular carcinoma in situ
- Invasive lobular carcinoma
Apart from these, there are some lesser common types of breast cancer like phyllodes tumor, angiosarcoma, Paget’s disease of the nipple, and inflammatory breast cancer
Inflammatory Breast Cancer
Inflammatory breast cancer accounts for approximately 1% to 5% of all breast cancer cases and is a very aggressive and rapidly progressive type of breast cancer. Although it doesn’t produce a tumor in the breast, cells block the lymph vessels draining the breast causes the affected breast to swell up and become dark.
Inflammatory breast cancer (IBC) develops in younger females of African descent. Due to its highly progressive nature, around 1 in 3 cases have already metastasized at the time of diagnosis. The diagnosis of IBC is usually made in the later stages.
What are the risk factors of Breast Cancer?
Breast cancer has many risk factors and they are divided into two types; modifiable and fixed risk factors. Many risk factors fall under both categories and contribute to the development and progression of breast cancer, however, the presence of any risk factor doesn’t guarantee that one will be developing the oncological pathology.
1. Fixed Risk Factors
Age: The risk of developing breast cancer increases with age, with most invasive breast cancers presenting in women over the age of 55 years. Breast cancer incidence increases after the age of 50 years with 2 cases of breast cancer per 100 in this specific age group.
Gender: Breast cancer shows a particular predilection to the female gender as it affects mostly women.
Genetic factors: Hereditary breast-ovarian cancer syndrome can cause breast cancer in less than 5 percent of the population through BRCA1 and BRCA2 mutations. BRCA1 and BRCA2 mutations make up for 90% of the total genetic influence with an 80% risk of breast cancer development in those affected. Genetic factors are the primary etiology in around 5-10 percent of total breast cancer incidences. Other genetic mutations responsible for the incidence of breast cancer are p53, PTEN, STK11, CHEK2, ATM, BRIP1, and PALB2. P53, PTEN, and STK11 mutations are associated with specific syndromes, namely Li-Fraumeni Syndrome, Cowden Syndrome, Peutz-Jeghers Syndrome respectively.
Family history: Although the majority of women who develop breast cancer do not have a family history, it does play a big role in the development of breast cancer. Having a first-degree female relative (mother, grandmother, sister) increases the risk of breast cancer in an individual.
It was found that women whose mothers had been diagnosed with breast cancer before the age of 50 had a 1.7 percent chance of developing it themselves whereas daughters of mothers diagnosed after the age of 50 had a 1.3 percent chance of developing breast cancer.
Those with a first-degree relative diagnosed with breast cancer during the age of 40-50 years have double the chances of being diagnosed with breast cancer when compared to the general population.
Personal history: The previous history of breast cancer in one breast increases the risk of breast cancer developing in the other breast or a different area of the same breast.
2. Modifiable Risk Factors
Obesity: Obesity is a common modifiable risk factor for breast cancer. However, the correlation between obesity and breast cancer is not linear. Excess fat in the midsection of the body, gained rapidly as an adult is more likely to be associated with the development of breast cancer than excessive fat in the lower body present since childhood.
Weight gain after menopause is especially related to the development of breast cancer.
More important than the BMI of an individual is what the person eats. Diet rich in fats along with high cholesterol levels is strongly associated with incidences of breast cancer.
Living a sedentary lifestyle with little to no physical exercise is also known to increase the risk of breast cancer.
Alcoholism: This, like obesity, is a common modifiable risk factor with even low to moderate consumption levels being associated with an increased incidence of breast cancer.
Smoking: Cigarette smoking is associated with cancer of many types, namely lung, and breast. The high risk of breast cancer development is usually due to the early initiation of smoking and heavy smoking. Long-term smokers have a 35-50 percent increased risk of developing breast cancer.
Menstrual factors: Estrogen is strongly associated with breast cancer development. Longer estrogen exposure is one of the risk factors for breast cancer which can be due to early menarche (the first menstrual period) and delayed menopause (the last menstrual period).
Reproductive factors: Research found that women who never gave birth as in carried a pregnancy full term or never got pregnant had a higher risk of developing breast cancer than those who had. Furthermore, women who had their first child after the age of 35 years have been shown to have a high risk of breast cancer development.
Hormone Replacement Therapy: As mentioned above, estrogen exposure is a major risk factor in the development of breast cancer. Women who take postmenopausal estrogen therapy to help with the symptoms of menopause are more likely to develop breast cancer due to increased estrogen exposure.
Radiation exposure: Women who had received chest or breast radiation therapy for cancer treatment before the age of 30 have a higher risk of developing breast cancer.
What is the pathophysiology of breast cancer?
Cancer occurs when cells lose their ability to undergo apoptosis or controlled cell death and keep on dividing. The accumulation of such cells gives rise to cancer. Cells have certain pathways to prevent early apoptosis which can get mutated via acquired or inherited mutations and result in no cell death, allowing these cells to multiply.
The same mechanism applies to the development of breast cancer where DNA and genetic mutations are associated with excessive estrogen exposure. The common inherited mutations are in p53, BRCA1, and BRCA2. As mentioned above these mutations result in syndromes that may present with ovarian, cervical, and breast cancer.
What is the classical presentation of breast cancer?
Breast cancer in its earlier stages does not present with any symptoms. The first symptom is usually a lump felt in the breast either during self-examination or physical examination by a doctor, however, it is important to note that not all lumps are cancer.
Lumps palpated in the breast or in the axillary region (armpit) are usually indicative of breast cancer. Apart from the presence of lumps, thickening, or enlargement of one breast over the other may also indicate breast cancer.
Nipple changes may also be present in breast cancer, especially inversion or inflammation. There might be nipple discharge other than breast milk that may or may not be bloody.
Skin changes are also a common presentation of breast cancer. The skin around the nipple may begin to peel off or have a scaly appearance or there may be dimpling of the skin covering the breast tissue. Red pitting all over the breast is also a sign of breast cancer.
Breast pain or pulling pain at the nipple is also a sign of breast cancer. Overall, any sudden change in the shape and size of the breast can be indicative of breast cancer and needs to be examined properly.
How can breast cancer be diagnosed?
A lump is usually palpated either by self-examination or by a physician, and further examination using a diagnostic mammogram or breast ultrasound may be recommended. Sometimes, an MRI may be suggested.
If the results of these examinations are inconclusive, a tissue sample is taken and analyzed.
The diagnosis of breast cancer is confirmed using microscopic analysis of the sample taken from the affected breast tissue. However, the above-mentioned exams and diagnostic approaches are applied before the biopsy is taken.
Usually, a Fine-needle aspiration biopsy (FNAB) is performed, however other options for biopsy include core biopsy, vacuum-assisted biopsy, or an excisional biopsy.
After confirming the diagnosis of breast cancer, breast cancer needs to be classified based on several factors and how they influence the prognosis.
Classification of breast cancer
The breast cancer classification system depends on various criteria for subtyping it into different categories. The major categories include classification of it based on the histopathological type of cancer, the grade of cancer, the stage of cancer, and the receptor status of cancer.
1. Histopathological Types
This refers to the microscopic analysis of the biopsy sample to study the histological involvement in the disease. This analysis helps a physician understand which cells the cancer is derived from. Usually, breast cancer arises in the ductal or lobular cells of the breast.
2. Grading of cancer
The grading of cancer depends on the difference between normal breast cells and cancerous breast cells. More specifically, the presence of differentiation (specific shape and size of cells pertaining to their specific function) helps grade cancer as low or high-grade cancer. Cancerous cells are not well differentiated.
The Nottingham system, also known as Bloom-Richardson-Elston (BRE) system, is used for grading of breast cancer. BRE system adds the scores for three criteria, namely; tubule formation, nuclear pleomorphism, and mitotic count, and gives the overall score.
Grading of cancer along with the prognosis is as follows:
- Grade 1 (well-differentiated). Best prognosis.
- Grade 2 (moderately differentiated). Medium prognosis.
- Grade 3 (poorly differentiated). Worst prognosis.
3. Staging of cancer
The staging of breast cancer uses TNM classification which is based on the size of the tumor(T), the involvement of axillary and neck lymph nodes (N), and whether the tumor has metastasized to other parts of the body (M).
Based on TNM classification, breast cancer can be TX, T0, Tis, T1, T2, T3, or T4 based on the size of the tumor, NX, N0, N1, N2, or N3 based on the number and size of the cancerous cells deposited on lymph nodes, and M0, M)(i+), and M1 based on metastasis of the cancerous cells.
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The overall staging depending on TNM classification is as follows:
- Stage 0: Tis
- Stage I: T1N0
- Stage II: T2N0, T3N0 T0N1, T1N1, or T2N1
- Stage III: Invasion into skin and/or ribs, matted lymph nodes, T3N1, T0N2, T1N2, T2N2, T3N2, AnyT N3, T4 any N, locally advanced breast cancer
- Stage IV: M1, advanced breast cancer.
4. Receptor Status of cancer
Cells in the breast have receptors on the surface that can bind to chemical messengers like hormones and activate the signal cascade. The presence of certain hormonal receptors can help understand the pathophysiology, determine treatment, and the prognosis of cancer. The receptors that are checked for are Estrogen Receptor (ER), Progesterone Receptor (PR), and HER/neu receptors. Based on the presence or absence of these receptors, breast cancer can be ER positive/negative, PR positive/negative, and HER positive/negative. If all three receptors are not found, then cancer can be classified as triple-negative/ basal-like breast cancer.
Can breast cancer be prevented?
Breast cancer has many modifiable risk factors, which can help prevent it. Living a healthier, more active life, and undergoing regular screenings can prevent or help diagnose breast cancer in the earliest stages.
Performing self-breast examinations regularly can help in the early diagnosis of any breast pathology, not just breast cancer. Similarly, undergoing regular screening using mammograms can help diagnose breast cancer earlier which can then be treated before it progresses.
Screening for breast cancer is recommended for all women with a moderate risk of developing breast cancer by the American College of Physicians (ACP). The guidelines are as follows:
- Women ages 40 to 49: No mammograms recommended
- Women ages 50 to 74: Biennial mammograms are recommended
- Women 75 and older: Mammograms are no longer recommended.
According to the American Cancer Society (ACS), annual breast cancer screening should be started from the age of 45 years, and from the age of 55 years, biennial mammograms must be performed to screen for breast cancer.
Women with BRCA1 and BRCA2 mutations may undergo preemptive treatment, also known as a prophylactic bilateral mastectomy, which is the removal of breast tissue before any lumps are found or cancer is diagnosed.
What is the treatment of breast cancer?
Treatment of breast cancer depends on the age of the patient, stage of cancer, and the general nature of cancer.
The most common treatment of breast cancer is surgery, which may be followed by chemotherapy or radiation, or in some cases, both may be applied.
1. Surgery: Surgery for breast cancer can range from a plain removal of the lump called lumpectomy to a radical mastectomy with prophylactic contralateral mastectomy. After the surgery to remove the tumor, lymph nodes that drain the breast may also be removed in a process called a sentinel node biopsy. These lymph nodes are then analyzed, and if they have cancer cells, axillary lymph node dissection is needed. If these nodes have no cancer cells, no further surgery is required.
2. Radiation therapy
3. Chemotherapy: Some doctors actually prefer their patients to undergo chemo before surgery in hopes that chemotherapy will shrink cancer and the surgery can be minimally invasive.
4. Hormone Therapy: Breast cancer with hormone receptors may be treated with hormone-blocking drugs against Estrogen and Progesterone that can reduce the hormones produced by the body, not allowing for further growth of cancerous cells.
5. Medications: Certain medications may be prescribed by a doctor for the treatment of breast cancer that works against the mutations in the cancer cells. Trastuzumab is a monoclonal antibody that inhibits the production of HER protein in the body and hence helps in the treatment of HER positive cancer.
The recent advances in the treatment of breast cancer and earlier diagnosis of it have helped increase the 5- year survival rate from 75.2% in 1975 to 90.6% between 2008 and 2014.
Recent research into Breast cancer
Investigations and researches are being performed with regards to treatment and screening methods of breast cancer to help improve the survival rate of breast cancer. According to the CDC website, many studies are also being performed regarding the socio-economic effects of breast cancer and the prevalence of breast cancer in different ethnicities.
Currently, gene therapy, target therapy, oncolytic virotherapy, and immunotherapy are being evaluated in clinical trials to check for their efficiency in treating breast cancer.
Nindrea, Ricvan Dana et al. “Breast Cancer Risk From Modifiable and Non-Modifiable Risk Factors among Women in Southeast Asia: A Meta-Analysis.” Asian Pacific journal of cancer prevention: APJCP vol. 18,12 3201-3206. 28 Dec. 2017, doi:10.22034/APJCP.2017.18.12.3201
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