Taking a look at BREAST CANCER
- Polelo Mawela
- Oct 19, 2022
- 25 min read
Breast cancer is a multifaceted disease involving environmental, genetic, and lifestyle risk factors. Breast cancer also represents a collection of clinically heterogeneous diseases ranging from indolent to aggressive. Several differences have been observed in breast cancer epidemiology between populations.
A Global Scope
In 2020, there were 2.3 million women diagnosed with breast cancer and 685 000 deaths globally. As of the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the past five years, making it the world’s most prevalent cancer.
Age-standardized breast cancer mortality in high-income countries dropped by 40% between the 1980s and 2020. Countries that have succeeded in reducing breast cancer mortality have been able to achieve an annual breast cancer mortality reduction of 2-4% per year. If an annual mortality reduction of 2.5% per year occurs worldwide, 2.5 million breast cancer deaths would be avoided between 2020 and 2040.
In Africa, breast cancer is responsible for one in four diagnosed cancers and one in five cancer deaths in women. Incidence marked variation exists in the reported incidence of breast cancer worldwide – from 95 to 100 cases per 100 000 persons in North America, Northern Europe, and Australia to 13.5 - 30 per 100,000 women in sub-Saharan Africa (SSA). The breast cancer incidence in Africa continues to increase and is projected to double by 2050.
Breast cancer is the most common cancer in women in the United States (US), except for skin cancers and has a prevalence rate of about 30% (or 1 in 3) of all new female cancers each year.
The American Cancer Society's (ACS) estimates for breast cancer in the United States for 2022 are:
About 287 850 new cases of invasive breast cancer will be diagnosed in women.
About 51 400 new cases of ductal carcinoma in situ (DCIS) will be diagnosed.
About 43 250 women will die from breast cancer.
Breast cancer mainly occurs in middle-aged and older women. The median age at the time of breast cancer diagnosis is 62.
According to US statistics the average risk of a woman developing breast cancer in her lifetime is about 13%. This means there is a 1 in 8 chance of developing breast cancer. In recent years, incidence rates have increased by 0.5% per year.
A South African Scope
The five leading types of cancer that indiscriminately afflict women in South Africa (SA) according to the 2019 National Cancer Registry (NCR) are: breast, cervical, colorectal, uterine cancer, and non-Hodgkin’s lymphoma. Apart from non-melanoma skin cancer, breast cancer is the most common cancer in women of all races, with a lifetime risk of 1 in 27 in SA, according to the 2019 National Cancer Registry (NCR).
Both breast and cervical cancer have been identified as a national priority with increasing incidences occurring.
Approximately 19.4 million women aged 15 years and older live at-risk of being diagnosed with breast cancer affecting women in SA the most.
Trends in Breast Cancer Deaths
Breast cancer is the second leading cause of cancer death in women. The chance that a woman will die from breast cancer is about 2.6% (1 in 39 chance).
Since 2007, breast cancer death rates have been steady in women younger than 50 but have continued to decrease in older women. From 2013 to 2018, the death rate went down by 1% per year.
These decreases are believed to be the result of detecting breast cancer earlier through screening and increased awareness, as well as better treatments.
Differences by Race & Ethnicity
Some variations in breast cancer can be seen between racial and ethnic groups, e.g.
The median age of diagnosis is slightly younger for black women (60 years old) compared to white women (63 years old).
Black women have the highest death rate from breast cancer. This is thought to be partially because about 1 in 5 black women with breast cancer have triple-negative breast cancer (TNBA) - more than any other racial/ethnic group.
Black women have a higher chance of developing breast cancer before the age of 40 compared to that of White women.
At every age, black women are more likely to die from breast cancer than any other race or ethnic group.
White and Asian/Pacific Islander women are more likely to be diagnosed with localized breast cancer than Black, Hispanic, and American Indian/Alaska Native women.
Asian/Pacific Islanders have the lowest death rate from breast cancer.
American Indian/Alaska Natives have the lowest rates of developing breast cancer.
The strategies for improving breast cancer outcomes depend on fundamental health system strengthening to deliver the treatments that are already known to work. These are also important for the management of other cancers and other non-malignant noncommunicable diseases, e.g., having reliable referral pathways from primary care facilities to district hospitals to dedicated cancer centres.
The establishment of reliable referral pathways from primary care facilities to district hospitals to dedicated cancer centres is the same approach as is required for the management of cervical cancer, lung cancer, colorectal cancer, and prostate cancer. To that end, breast cancer is an “index” disease whereby pathways are created that can be followed for the management of other diseases.
The objective of the WHO Global Breast Cancer Initiative (GBCI) is to reduce global breast cancer mortality by 2.5% per year, thereby averting 2.5 million breast cancer deaths globally between 2020 and 2040. Reducing global breast cancer mortality by 2.5% per year would avert 25% of breast cancer deaths by 2030 and 40% by 2040 among women under 70 years of age.
The three pillars toward achieving these objectives are: health promotion for early detection; timely diagnosis; and comprehensive breast cancer management.
Signs & Symptoms
Breast cancer most commonly presents as a painless lump or thickening in the breast. It is important that women finding an abnormal lump in the breast consult a health practitioner without a delay of more than 1-2 months even when there is no pain associated with it. Seeking medical attention at the first sign of a potential symptom allows for more successful treatment.
Generally, symptoms of breast cancer include:
A breast lump or thickening.
Alteration in size, shape, or appearance of a breast.
Dimpling, redness, pitting or other alteration in the skin.
Change in nipple appearance or alteration in the skin surrounding the nipple (areola); and/or
Abnormal nipple discharge.
There are many reasons for lumps to develop in the breast, most of which are not cancer. As many as 90% of breast masses are not cancerous. Non-cancerous breast abnormalities include benign masses like fibroadenomas and cysts as well as infections.
Breast cancer can present in a wide variety of ways, which is why a complete medical examination is important. Women with persistent abnormalities (generally lasting > one month) should undergo tests including imaging of the breast and in some cases a biopsy to determine if a mass is malignant or benign.
Breast cancers may spread to other areas of the body and trigger other symptoms. Often, the most common first detectable site of spread is to the lymph nodes under the arm although it is possible to have cancer-bearing lymph nodes that cannot be felt.
Over time, cancerous cells may spread to other organs including the lungs, liver, brain, and bones giving rise to new cancer-related symptoms such as bone pain or headaches.
Early breast cancer is usually asymptomatic. As a breast cancer tumour grows, it can result in breast changes. Common changes include:
• A lump or thickening in or near the breast or in the armpit area.
• A change in the size or shape of the breast.
• Dimpling or puckering in the skin of the breast.
• The nipple becoming inverted.
• Abnormal discharge from the nipple.
• Scaly, red, or swollen skin on the breast, nipple, or areola.
• The skin of the breast taking on an orange peel look or feel.
Warning Signs Breast Cancer
Source: https://cansa.org.za/breast-cancer/ accessed: 24 September 2022
A particular challenge facing all Primary Health Care (PHC) providers is the overlap between cancer symptoms and symptoms arising from common local health conditions, e.g., infections and other conditions with symptoms like breast cancer. For example, symptoms such as skin induration, puckering and ulceration can also occur in women with a breast abscess, and with lactational and non-lactational breast infections. Lipodystrophy, a side-effect of some antiretroviral therapy (ART), results in a redistribution of body fat with loss over limbs and gain in various sites including the breast. Symptoms of breast cancer in patients on ART may thus be misattributed to lipodystrophy and could contribute to a delay in timely diagnosis.
Inherited Gene Changes & BRCA1 & BRCA2 Genes
Some gene mutations are inherited. Certain inherited gene changes can significantly increase the risk for developing certain cancers and are linked to many of the cancers that run in some families. For instance, the BRCA genes (BRCA1 and BRCA2) are tumour suppressor genes. When one of these genes mutates, it no longer suppresses abnormal cell growth, with the result in the onset of cancer. A change in one of these genes can be hereditary.
Women have already begun to benefit from advances in understanding the genetic basis of breast cancer. Genetic testing (e.g., the presence of mutated BRCA1/2 genes) can identify some women who have inherited this kind of mutations in the BRCA1 or BRCA2 tumour suppressor genes as well as other less common genes such as PALB2, ATM, or CHEK2.
These women can then take steps to reduce their risk of breast cancer by increasing breast awareness and following appropriate screening recommendations to help identify cancer at an earlier and more treatable stage. Since these mutations are also often associated with other cancers (besides breast), women with these mutations might also consider early screening and preventive actions for other cancers, e.g., ovarian cancer.
Mutations in tumour suppressor genes like the BRCA genes are considered “high penetrance” because they often lead to cancer. Although many women with high penetrance mutations develop cancer, most cases of cancers (including breast cancer) are not caused by this kind of mutation.
More often, “low-penetrance” mutations or gene variations are a factor in the development of cancer. These genes can affect hormone levels, metabolism, or other factors results in an impacted risk for breast cancer. These genes might also cause an inherited risk of developing of breast cancer.
Acquired gene changes
Most gene mutations linked to breast cancer are acquired. This means the change takes place in breast cells during a person's life rather than having been inherited or born with them. Acquired DNA mutations take place over a period and are only in the breast cancer cells.
These acquired mutations of oncogenes and/or tumour suppressor genes may result from other factors, like radiation or carcinogens while others can be random events of changes inside of the cell, without having an external cause.
Increasing rates of breast cancer cases are particularly alarming within most sub-Saharan African countries e.g., biologically aggressive triple-negative breast cancer (TNBC, tumours that are negative for the oestrogen receptor [ER], progesterone receptor [PR], and the protein HER2/neu) phenotype within the African American community and have fuelled speculation that African ancestry itself might be associated with hereditary susceptibility for specific patterns of breast cancer.
Molecular tests for gene changes
In some cases, testing for specific gene changes in the breast cancer cells could aid in using immunotherapeutic cancer treatment medication.
Some genes tests include the following:
Testing for BRC1 and BRCA2 mutations alone: For women with an advanced HER2- breast cancer, testing for a hereditary BRCA1 or BRCA2 mutation is done.
Testing for PIK3CA gene mutation alone: Cancer cells that have a certain structure like that of the PI3K protein aids in their growth. This protein comes from an abnormal PIK3CA gene change.
Microsatellite Instability (MSI) and Mismatch Repair (MMR) testing: These kinds of tests are done to determine high levels of gene changes called microsatellite instability (MSI). Testing is also be done to determine if the cancer cells have changes in any of the mismatch repair (MMR) genes e.g., MLH1, MSH2, MSH6, and PMS2.
Tumour Mutational Burden (TMB): TMB is a measure of the number of gene mutations inside the cancer cells.
Testing for NTRK fusion genes: Some breast cancer cells can have changes in one of the NTRK genes. These gene changes can result in cancer development.
Breast Cancer Stages & Grading
After being diagnosed with breast cancer it is important to know what the grade and stage of the cancer is as this is indicative of the spreading of the cancer in the human body. This also aids in which treatment modalities for the different kinds of stages and grading of the cancer cells should be considered.
(a) Grading tumours as grades (0-IV)
Cancer cells are given a grade upon removal of the tumour. Grading is based on the amount of cancer cells that appear as normal cells. Grading is useful in the prognosis and aids in which treatment modality should be used.
· Grade 0 indicates that the cancer is in situ.
Grade I indicate that the cancer is slower in growth and is less likely to spread.
Grade II indicates that the cancer is growing faster than a grade 1 cancer but slower than a grade 3 cancer.
Grade III is interpreted as a faster-growing cancer which is more likely to spread.
Grade IV is the more advanced kind of cancer.
Three features of the invasive breast cancer cell are studied and given a score. The scores are then added to get a number between 3 and 9 which is used to get a grade of I, II, or III.
(b) Grading tumours as: “well differentiated, moderately differentiated, and poorly differentiated’
Grade 1 or “well differentiated” is scored: 3, 4, or 5. The cells are slower-growing, and appears more like normal breast cells.
Grade 2 or moderately “differentiated” (score 6 and 7). The cells are slower growing and appears more like cells like those seen in between grades 1 and 3.
Grade 3 or “poorly differentiated” (score 8 and 9). The cells look very different from normal cells and grows and spreads faster than the above-mentioned tumour grading.
Grading ductal carcinoma in situ (DCIS) is also graded on how abnormal the cancer cells appear and has a similar grading system to that used for invasive breast cancer (see above).
Grade 1 or low-grade DCIS. The cells are slower growing and appears more like normal breast cells. These cells’ receptors are oestrogen receptor (ER+) positive and progesterone receptor (PR+).
Grade 2 or intermediate grade. The cells are growing at a speed of and appears like cells between grades 1 and 3.
Grade 3 or high grade. The cancer cells look are not similar from normal cells and are growing faster. These cells tend not to have ER- and PR- receptors.
High grade DCIS is often more likely to turn into invasive breast cancer.
Necrosis is also noted. If necrosis exists, it implies that the tumour growth is fast. The term “comedo necrosis” is used if a breast duct is filled with dead and dying cells. Comedo necrosis is often linked to a high grade of DCIS and has a higher chance of developing into invasive breast cancer.
(c) Breast cancer stage grouping according to the American Joint Committee on Cancer (AJCC)
Another staging system used for breast cancer is the American Joint Committee on Cancer (AJCC) TNM system.
The most recent AJCC system, effective January 2018, has both clinical and pathologic staging systems for breast cancer:
The pathologic stage (also called the surgical stage) is determined by examining the tissue which was removed.
Should surgery not be possible immediately or not at all, the cancer will be given a clinical stage instead. This is based on the results of a physical exam, biopsy, and imaging tests. The clinical stage is used to determine the treatment regimen. In some instances, the cancer might have spread further than the clinical stage estimates and may not predict the patient’s outlook as accurately as a pathologic stage.
In both above staging systems, seven key pieces of information are used:
The extent (size) of the tumour (T): How large is the cancer? Has it grown into nearby areas?
The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes? If so, how many?
The spread (metastasis) to distant sites (M): Has the cancer spread to distant organs such as the lungs or liver?
(O)estrogen Receptor (ER) status: Does the cancer have the protein called an oestrogen receptor?
Progesterone Receptor (PR) status: Does the cancer have the protein called a progesterone receptor?
HER2 status: Does the cancer produce a significant amount of the of the protein called HER2?
Grade of the cancer (G): How much do the cancer cells look like normal cells?
Once all these factors have been determined, the above information is then combined in a process called stage grouping to assign an overall stage.
Details about the first three factors/staging (TNM) are listed below. However, the additional information about the ER, PR, and HER2 status along with a grade has made stage grouping for breast cancer more complex than for other cancers.
Details of the TNM (define) staging system
Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. The categories below use the pathologic (surgical) definitions.
T categories for breast cancer
T followed by a number from 0 to 4 describes the main (primary) tumour’s size and if it has spread to the skin or to the chest wall under the breast. Higher T numbers mean a larger tumour and/or wider spread to tissues near the breast.
TX: Primary tumour cannot be assessed.
T0: No evidence of primary tumour.
Tis: Carcinoma in situ DCIS, or Paget disease of the breast with no associated tumour mass.
T1: (includes T1a, T1b, and T1c): Tumour is 2 cm or less across.
T2: Tumour is > 2 cm but not > 5 cm across.
T3: Tumour is > 5 cm across.
T4: (includes T4a, T4b, T4c, and T4d): Tumour of any size growing into the chest wall or skin. This includes inflammatory breast cancer (IBC).
N categories for breast cancer
N followed by a number from 0 to 3 indicates whether the cancer has spread to lymph nodes near the breast and, if so, how many lymph nodes are involved.
Lymph node staging for breast cancer is done microscopically.
It’s not yet clear how much cancer in the lymph node is needed to see a change in outlook or treatment. Currently a amount of cancer cells should contain at least 200 cells or be > 0.2 mm across for it to change the N stage.
An area of cancer spread that is > 0.2 mm (or < 200 cells) doesn't change the stage but is recorded with abbreviations (i+ or mol+) which aids in specifying the type of test should be used to find the spread.
If the area of cancer spread is at least 0.2 mm (or 200 cells), but still not > 2 mm, it is called a micro-metastasis (one mm). Micro-metastases are counted only if there are not any larger areas of cancer spread. Areas of cancer spread > 2 mm are known to influence outlook and do change the N stage. These larger areas are termed called macro-metastases but are more often just called metastases.
NX: Nearby lymph nodes cannot be assessed (for example, if they were removed previously).
N0: Cancer has not spread to nearby lymph nodes.
N0(i+): The area of cancer spread contains > 200 cells and is > 0.2 mm. The abbreviation "i+" means that a small number of isolated tumour cells are seen in routine stains or when immunohistochemistry (IHC) was used.
N0(mol+): Cancer cells cannot be seen in underarm lymph nodes (even using special stains), but traces of cancer cells were detected using a technique called Reverse Transcription Polymerase Chain Reaction (RT-PCR).
N1: Cancer has spread to one to three axillary lymph node(s), and/or cancer is found in internal mammary lymph nodes (those near the breastbone) on sentinel lymph node biopsy.
N1mi: Micrometastases in the lymph nodes under the arm. The areas of cancer spread in the lymph nodes are at least 0.2mm across, but not larger than 2mm.
N1a: Cancer has spread to one to three lymph nodes under the arm with at least one area of cancer spread > 2 mm across.
N1b: Cancer has spread to internal mammary lymph nodes on the same side as the cancer, but this spread could only be found on sentinel lymph node biopsy (e.g., it did not cause the lymph nodes to become enlarged).
N1c: Both N1a and N1b apply.
N2: Cancer has spread to four to nine lymph nodes under the arm, or cancer has enlarged the internal mammary lymph nodes
N2a: Cancer has spread to four to nine lymph nodes under the arm, with at least one area of cancer spread > 2 mm.
N2b: Cancer has spread to one or more internal mammary lymph nodes, causing them to become enlarged.
N3: Any of the following:
N3a: either:
Cancer has spread to 10 or more axillary lymph nodes, with at least one area of cancer spread > 2 mm,
OR
Cancer has spread to infraclavicular nodes, with at least one area of cancer spread > 2 mm.
N3b: either:
Cancer is found in at least one axillary lymph node (with at least one area of cancer spread > 2 mm) and has enlarged the internal mammary lymph nodes,
OR
Cancer has spread to four or more axillary lymph nodes (with at least one area of cancer spread > 2 mm), and to the internal mammary lymph nodes on sentinel lymph node biopsy.
N3c: Cancer has spread to the supraclavicular nodes on the same side of the cancer with at least one area of cancer spread >2 mm.
M categories for breast cancer
M followed by a 0 or 1 indicates whether the cancer has spread to distant organs e.g., the lungs, liver, or bones.
M0: No distant spread is found on x-rays (or other imaging tests) or by physical exam.
cM0(i+): Small numbers of cancer cells are found in blood or bone marrow, or tiny areas of cancer spread (no larger than 0.2 mm) are found in lymph nodes away from the underarm, collarbone, or internal mammary areas.
M1: Cancer has spread to distant organs (most often to the bones, lungs, brain, or liver) as seen on imaging tests or by physical exam, and/or a biopsy of one of these areas proves cancer has spread and is > 0.2 mm.
Tests for certain proteins on tumour cells
Laboratory tests can be used to determine certain proteins on the cancer cells. These include the following:
(a) Breast Cancer Hormone Receptor Status
All breast cancers are tested for hormone receptor proteins. These include testing for (o)estrogen receptor (ER) and progesterone receptor (PR) proteins. Breast cancer cells that are removed can also be tested to determine if there are proteins that are ER or PR. Upon attaching to the endogenous hormones oestrogen and progesterone stimulates cancer growth.
Cancers are called hormone receptor-positive (HR+) or hormone receptor-negative (HR-) based on whether they have ER and/PR.
Breast cancer cells may have one, both or none of these receptors:
ER-positive (ER+) is defined by the breast cancer cells having oestrogen receptors and are called ER-positive (ER+) cancers.
PR-positive (PR+) is defined by the breast cancer cells having progesterone receptors are called PR-positive (PR+) cancers.
Hormone receptor-positive (HR+) is defined by the breast cancer cells having one or both ER and PR and is termed hormone-receptive positive (HR+) breast cancers.
Hormone receptor-negative (HR-) is defined by the breast cancer cells not having ER and PR, and its termed as hormone-receptor negative (HR-).
Keeping the hormones oestrogen and progesterone from attaching to the receptors can assist in preventing the cancer from growing and spreading.
The significance of determining the hormone receptor status
An immunohistochemistry (IHC) test is used to determine the hormone receptor status, and this can aid in the treatment modality for the breast cancer.
The identification of the hormone receptor status of the cancer aids in the treatment modality thereof. If cancer cells have one or both hormone receptors, hormone therapy medication can be used to either lower oestrogen levels or stop oestrogen from acting on breast cancer cells. This kind of treatment is helpful for HR+ breast cancers, but it doesn’t work on tumours that are hormone receptor-negative (both ER- and PR-negative).
All invasive breast cancers should be tested for both hormone receptors either via a biopsy or upon removal of the tumour.
About three of four breast cancers have at least one of these receptors. This percentage is higher in older women compared to younger women. Ductal carcinoma in situ (DCIS) should also be checked for hormone receptors.
The determination of the hormonal receptor status will indicate whether the tumour is hormone positive or negative. If the results indicate that > 1% of the cells test positive, it can be interpreted that the tumour has oestrogen and/or progesterone receptors. If the test is negative, it implies that the tumour is hormone receptor negative.
Hormone receptor-positive/hormone-positive (HR+) cancer cells have either ER or PR or both. These breast cancers can be treated with hormone therapy medication which lowers oestrogen levels or block oestrogen receptors.
Hormone receptor-positive/hormone-positive cancer cells tend to grow at a slower pace when compared to hormone receptor-negative cancers. Women with hormone receptor-positive cancers tend to have a better life expectancy short-term but stand the change of having a remission of breast cancer.
Hormone receptor-negative/hormone-negative (HR-) cancer cells does not have ER or PRs. Treatment with hormone therapy medication is not successful in the treatment for these kind of breast cancers. These kind of breast cancers tend to grow faster compared to HR+ cancers. The remittance of these kind of cancer cells is often within in the first few years of diagnosis. Hormone receptor-negative (HR-) cancers are more common in women who have not yet gone through menopause.
Triple-negative breast cancer cells (TNBC) does not have ER or PR and does not produce a lot of HER2 proteins. These cancers are more common in women > 40 years of age, who are Black, or who have a mutation in the BRCA1 gene. Triple-negative breast cancers grow and spread faster than most other types of breast cancer. Because the cancer cells does not have hormone receptors, hormone therapy is not helpful in treating these cancers, and since they don’t have a large amount of HER2 proteins, medications that target HER2 is not very successful.
Women with African ancestry in western, sub-Saharan Africa and in the United States represent a population subset facing an increased risk of being diagnosed with aggressive phenotypes of breast cancer which are ER- PR- and HER2/neumarker (ne) negative (TNBC).
Triple-positive breast cancer cells are ER+, PR+, and HER2+. These cancers can be treated with hormonal medication as well as medication aimed at targeting the HER2 protein.
(b) Human Epidermal Growth Factor Receptor 2 (HER2) protein
Testing for this protein is to determine the quantity of HER2 production. If it is not clear how much HER2 protein is present, the breast cancer cells may then undergo molecular testing for gene changes to determine how many copies of the HER2 gene are produced.
Human Epidermal Growth Factor Receptor 2 (HER2) is a protein that causes breast cancer cells to develop at a fast rate. Breast cancer cells with higher-than-normal levels of HER2 are called HER2-positive (HER+). These cancers tend to grow and spread faster than breast cancers which are HER2-negative (HER-).
About 15% to 20% of breast tumours have higher levels of HER2 and is termed as HER+.
Interpretation of Human Epidermal Growth Factor Receptor 2 (HER2) testing
The results of HER2 testing will determine which treatment options should be considered.
An IHC test is often done first.
If the IHC result is 0, the cancer is considered HER2-.
If the IHC result is 1+, the cancer is considered HER2-
If the IHC result is 2+, the HER2 status of the tumour is not clear and is termed "equivocal" and needs to be tested with the Fluorescence In Situ Hybridisation (FISH) test to clarify the result.
If the IHC result is 3+, the cancer is HER2+.
Some breast cancers that have an IHC result of 1+ or an IHC result of 2+ along with a negative FISH test and is called HER2-low cancers.
Triple-negative breast cancer tumours (TNBC) don’t have a lot of HER2 and do not have oestrogen or progesterone receptors. They are termed: HER2-, ER-, and PR-negative.
Triple-positive breast cancer tumours (TPBC) are HER2+, ER+, and PR+.
(c) Programmed death-ligand 1 (PD-L1) protein
Breast cancer patients who present with advanced or metastatic TNBC can also consider being tested for the PD-L1 protein. The presence of this protein indicates the likelihood of response to treat the breast cancer versus the treatment with certain immunotherapy medications along with chemotherapy.
Management of Breast Cancer
Breast cancer treatment can be highly effective, achieving survival probabilities of 90% or higher, particularly when the disease is identified early. Treatment generally consists of surgery and radiation therapy for control of the disease in the breast, lymph nodes and surrounding areas (locoregional control) and systemic therapy (anti-cancer medicines given orally or intravenously) to treat and/or reduce metastasis.
Anti-cancer medicines include endocrine (hormone) therapy, chemotherapy and in some cases targeted biologic therapy (antibodies).
(a) Pharmacological management
Medical treatments for breast cancers, which may be given before (“neoadjuvant”) or after (“adjuvant”) surgery, is based on the biological subtyping of the cancers. Cancer that expresses the ER and/or PR are likely to respond to endocrine (hormonal) medications such as tamoxifen or aromatase inhibitors. These medicines are taken orally for 5-10 years and reduce the chance of recurrence of these “hormone-positive” cancers by nearly half. Endocrine therapies can cause symptoms of menopause but are generally well tolerated.
Cancers that do not express ER or PR are HR- and need to be treated with chemotherapy unless the cancer is limited in size. The chemotherapy regimens available today are very effective in reducing the chances of cancer spread or recurrence and are generally given as outpatient therapy. Chemotherapy for breast cancer generally does not require hospital admission in the absence of complications.
Breast cancers may independently overexpress the HER-2/neu oncogene protein. These HER-2+ cancers are amenable to treatment with targeted biological agents such as trastuzumab. These biological agents are very effective but also costly, due to their nature of being antibodies rather than chemicals. When targeted biological therapies are given, they are combined with chemotherapy to make them effective as a treatment modality.
Cost and access to medication(s)
Hormonal therapy for breast cancer is one of the most available treatment options even in poorer countries. Many companies supply a less costly version of tamoxifen at a very low cost making it readily available and, in some countries, available free of charge. Unlike tamoxifen, the access and availability of aromatase inhibitors is restricted in most of Africa.
Choice of medication
In Africa, patients are more likely to be ER-, rendering tamoxifen ineffective in disease control if prescribed for all breast cancer patients. A recent meta-analysis of hormone receptor status of breast cancer patients in Africa indicates that more than half of African women have HR+ breast cancer, disputing the poor receptor status in most breast cancer cases.
Compliance to hormone therapy
Non-adherence to hormone treatment is a common worldwide problem and ranges 30–72% for adherence and discontinuation. Small studies from Nigeria and South Africa report 25 and 36% non-adherence rates for tamoxifen which is comparable to data from developed countries.
(b) Radiotherapy
Radiotherapy also plays a very important role in treating breast cancer. With early-stage breast cancers, radiation can prevent a woman having to undergo a mastectomy. With later stage cancers, radiotherapy can reduce cancer recurrence risk even when a mastectomy has been performed. For advanced stage of breast cancer, radiation therapy may reduce the likelihood of dying of the disease.
The effectiveness of breast cancer therapies depends on the full course of treatment. Partial treatment is less likely to lead to a positive outcome.
Nonpharmacological management/preventative measures
Breast Examinations
While not all breast lumps indicate cancer, they should be investigated, especially if accompanied by other changes in breasts or the under-arm area, e.g., lumps, texture changes, thickening, dimpling, changes in shape or size of nipples or breasts, tenderness, discharge, rash or swelling, or one breast suddenly being slightly larger than the other.
(a) Breast Self-Examination (BSE)
Research has shown that a regular BSE, plays an important role in discovering breast cancer early, compared to finding a breast lump by chance.
A BSE should be done once a month, preferably at the same time of day, following a woman’s menstrual cycle, (seven to 10 days after menstruating) and repeated monthly with the same time interval.
The following guidelines can be provided to patients during breast awareness events.
Asking questons such as: “Do you feel or see any change in your breasts or underarms? If there are changes arrange for a Clinical Breast Examination (CBE) at a local Cancer Association of South Africa (CANSA) Care Centre, primary health care centre or health practitioner” can prove a valuable communication tool during discussions of a HCP and a patient, especially during breast cancer awareness campaigns or events. This can then be followed up by instructions:
In the mirror: In front of a mirror, check for any changes in the normal look and feel of your breasts, such as dimpling, size difference or nipple discharge. Inspect in four ways: arms at the side; arms over head; firmly pressing hand on hips and bending forward
Lying down: Lie on your back with a pillow under your right shoulder and your right hand under your head. With the three middle fingers on your left hand make small circular motions, follow an up and down pattern over the entire breast area, under the arms and up to the shoulder bone pressing firmly. Repeat using right hand on left breast
While bathing: With your right arm raised, check your right breast with a soapy left hand and fingers flat using the method described under “lying down”, Repeat on the other side.
(b) Clinical Breast Examinations (CBE) and screening tests
A CBE is a visual and manual examination of the entire breast, from the collarbone to the bra line, and from the armpit to the breastbone. It is advisable to have a CBE as part of your annual medical check-up.
Women are entitled to an annual CBE when visiting PHC centres (according to the National Department of Health’s Breast Cancer Control Policy).
Should any abnormalities be detected referral should be sought for further testing by a medical professional.
(c) Mammograms
Mammograms are used for detecting breast cancer at an early stage. Finding breast cancers early with mammography also implies that many more women being treated for breast cancer, can keep their breasts. When a mammogram is done early, localised cancers can be removed without resorting to a mastectomy.
Women from the age of 40 should go for an annual mammogram, for purposes of non-symptomatic breast screening. Women 55 years and older, should have a mammogram every two years – or if they choose, continue with an annual mammogram. Women, who have other risk factors such as mutated BRCA1/2 ne genes, should be referred for an annual mammogram.
(d) MammaPrint (Genomic Testing)
The MammaPrint test is a genomic test that analyses the activity of certain genes in early-stage breast cancer. Research suggests the MammaPrint Test may eventually be widely used to assist in make treatment decisions based on the cancer’s risk of recurrence within 10 years after diagnosis.
It can help some breast cancer patients in avoiding chemotherapy treatment.
Only a surgeon, medical oncologist, radiation oncologist, pathologist can request for genomic testing.
(e) Surgical invasive procedures
Previously all breast cancers were treated surgically by a mastectomy. However, most breast cancers currently can be treated with a smaller procedure called a “lumpectomy” or partial mastectomy, in which only the tumour is removed from the breast. In these cases, radiation therapy to the breast is generally required to minimize the chances of recurrence in the breast.
Lymph nodes are removed at the time of cancer surgery for invasive cancers. Complete removal of the lymph node bed under the arm (complete axillary dissection) in the past was thought to be necessary to prevent the spread of cancer. A smaller lymph node procedure called “sentinel node biopsy” is now a preferred option with fewer complications. It uses dye and/or a radioactive tracer to find the first few lymph nodes to which cancer could spread from the breast.
Risk factors
Approximately half of breast cancers develop in women who have no identifiable breast cancer risk factor other than gender (female) and age (> 40 years). Certain factors increase the risk of breast cancer e.g., increasing age, obesity, harmful use of alcohol, family history of breast cancer, history of radiation exposure, reproductive history (such as age that menstrual periods began and age at first pregnancy), tobacco use and postmenopausal hormone therapy.
Female gender is the strongest breast cancer risk factor. A family history of breast cancer increases the risk of breast cancer, but most women diagnosed with breast cancer do not have a known family history of the disease. Lack of a known family history does not necessarily imply that a woman is at reduced risk.
Certain inherited “high penetrance” gene mutations greatly increase breast cancer risk, the most dominant being mutations in the genes: BRCA1, BRCA2 and PALB-2. Women found to have mutations in these major genes could consider risk reduction strategies such as a double mastectomy. Consideration of such a highly invasive approach only concerns a very limited number of women and should be carefully evaluated considering all alternatives and should not be rushed.
The American Actor and Director, Angelina Jolie, opted for a preventive double mastectomy after discovering that she has a significant percentage of the mutated BRCA1 gene and that this would increase her risk sharply for developing breast cancer and ovarian cancer. She also had a family history of breast cancer.
Behavioural choices and related interventions that reduce the risk of breast cancer include, but is not limited to the following:
Prolonged breastfeeding.
Regular physical activity.
Weight control.
Avoidance of harmful use of alcohol.
Avoidance of exposure to tobacco smoke.
Avoidance of prolonged use of hormones and
Avoidance of excessive radiation exposure.
The following broad dietary guidelines can be used to decrease the risk of breast cancer. Apart from not smoking, and being as active as possible, the following (broad) nutritional guidelines can assist breast cancer survivors:
Increase intake of fresh fruits (in season), vegetables and whole grains.
Limit fat intake to > 30 % of kilojoules – especially animal fats.
Reduce (minimise) the intake of cured, pickled, smoked, and processed foods.
By providing public health education to improve awareness among women of the signs and symptoms of breast cancer and, together with their families, understand the importance of early detection and treatment, more women would possibly consult medical practitioners when breast cancer is first suspected and/or may be at an advanced stage. This is possible even in the absence of mammographic screening which is impractical in many countries at the present time.
Public education needs to be combined with health worker education about the signs and symptoms of early breast cancer so that women are referred to diagnostic services when appropriate.
Cancer Association of South Africa (CANSA)
• The local CANSA Care Centre can offer breast cancer patients and their families care and support. This includes the following: medical equipment hires, wigs, counselling, support groups, online support groups and resources, as well as CANSA Care Homes where patients receiving treatment far from home can stay during treatment.
• The Cancer Association of South (CANSA) staff can also provide guidance via the public health care system.
• Access the ‘Buddies for Life’ online lifestyle publication and find tips for breast cancer survivors.
• Metastatic Breast Cancer (MBC) patients can join the email support programme for weekly support or contact Abeda Steenkamp asteenkamp@cansa.org.za to be included in the MBC WhatsApp Support group.
• Joining of the CANSA ‘Champions of Hope’ Facebook Group: https://web.facebook.com/groups/ChampionsofHope/?_rdc=1&_rdr accessed: 24 September 2022
• CANSA also provides a counselling service dedicated to providing advice to cancer survivors. Call the Help Desk on 0800 22 66 22 to make an appointment for Tele Counselling or email: counselling@cansa.org.za. The service is free of charge and available in seven languages.
• Other CANSA contact details are:
Cell phone numbers: 072 197 9305 (English and Afrikaans), 071 867 3530 (isiXhosa, isiZulu, siSwati, Sesotho, and Setswana) and for general enquiries, email: info@cansa.org.za.
References:
American Cancer Society (ACA). https://www.cancer.org/ accessed: 01 October 2022
The Breast Cancer Association of South Africa (CANSA). https://cansa.org.za/ accessed: 01 October 2022
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Complier: Dr. Liesl Brown, BPharm, MSc (Pharm) Cum Laude, PhD
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