Breast cancer

Introduction

Breast cancer arises in the lining cells (epithelium) of the ducts (85%) or lobules (15%) in the glandular tissue of the breast. Initially, the cancerous growth is confined to the duct or lobule (“in situ”) where it generally causes no symptoms and has minimal potential for spread (metastasis).

Over time, these in situ (stage 0) cancers may progress and invade the surrounding breast tissue (invasive breast cancer) then spread to the nearby lymph nodes (regional metastasis) or to other organs in the body (distant metastasis).  If a woman dies from breast cancer, it is because of widespread metastasis.  

Breast cancer treatment can be highly effective, especially when the disease is identified early. Treatment of breast cancer often consists of a combination of surgical removal, radiation therapy and medication (hormonal therapy, chemotherapy and/or targeted biological therapy) to treat the microscopic cancer that has spread from the breast tumor through the blood. Such treatment, which can prevent cancer growth and spread, thereby saves lives.

Scope of the problem

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 5 years, making it the world’s most prevalent cancer. There are more lost disability-adjusted life years (DALYs) by women to breast cancer globally than any other type of cancer.  Breast cancer occurs in every country of the world in women at any age after puberty but with increasing rates in later life.  

Breast cancer mortality changed little from the 1930s through to the 1970s.  Improvements in survival began in the 1980s in countries with early detection programmes combined with different modes of treatment to eradicate invasive disease.

Who is at risk?

Breast cancer is not a transmissible or infectious disease.  Unlike some cancers that have infection-related causes, such as human papillomavirus (HPV) infection and cervical cancer, there are no known viral or bacterial infections linked to the development of breast cancer.

Approximately half of breast cancers develop in women who have no identifiable breast cancer risk factor other than gender (female) and age (over 40 years).  Certain factors increase the risk of breast cancer including 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.

Behavioural choices and related interventions that reduce the risk of breast cancer include:

• 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.

Unfortunately, even if all of the potentially modifiable risk factors could be controlled, this would only reduce the risk of developing breast cancer by at most 30%.

Female gender is the strongest breast cancer risk factor.  Approximately 0.5-1% of breast cancers occur in men. The treatment of breast cancer in men follows the same principles of management as for women.

Family history of breast cancer increases the risk of breast cancer, but the majority of women diagnosed with breast cancer do not have a known family history of the disease. Lack of a known family history does not necessarily mean 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 surgical removal of both breasts. Consideration of such a highly invasive approach only concerns a very limited number of women, should be carefully evaluated considering all alternatives and should not be rushed.

Signs and 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 more than one month) should undergo tests including imaging of the breast and in some cases tissue sampling (biopsy) to determine if a mass is malignant (cancerous) or benign.  

Advanced cancers can erode through the skin to cause open sores (ulceration) but are not necessarily painful. Women with breast wounds that do not heal should have a biopsy performed.  

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. Once they reach these sites, new cancer-related symptoms such as bone pain or headaches may appear.

Treatment

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 by mouth or intravenously) to treat and/or reduce the risk of the cancer spreading (metastasis). Anti-cancer medicines include endocrine (hormone) therapy, chemotherapy and in some cases targeted biologic therapy (antibodies).

In the past, all breast cancers were treated surgically by mastectomy (complete removal of the breast). When cancers are large, mastectomy may still be required. Today, the majority of breast cancers can be treated with a smaller procedure called a “lumpectomy” or partial mastectomy, in which only the tumor 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 procedures called “sentinel node biopsy” is now preferred as it has 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.

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 express the estrogen receptor (ER) and/or progesterone receptor (PR) are likely to respond to endocrine (hormone) therapies 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 “hormone receptor negative” and need to be treated with chemotherapy unless the cancer is very small. 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 a molecule called the HER-2/neu oncogene. These “HER-2 positive” cancers are amenable to treatment with targeted biological agents such as trastuzumab. These biological agents are very effective but also very expensive, because they are antibodies rather than chemicals. When targeted biological therapies are given, they are combined with chemotherapy to make them effective at killing cancer cells.

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, in some circumstances, 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.

Challenges

Survival of breast cancer for at least 5 years after diagnosis ranges from more than 90% in high-income countries, to 66% in India and 40% in South Africa. Early detection and treatment has proven successful in high-income countries and should be applied in countries with limited resources where some of the standard tools are available. The great majority of drugs used for breast cancer are already on the WHO Essential Medicines List (EML).  Thus, major global improvements in breast cancer can result from implementing what we already know works.

Global impact

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.  

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 (NCDs).  For example, 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 centers 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.

WHO response

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.  

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 consult medical practitioners when breast cancer is first suspected, and before any cancer present is advanced. This is possible even in the absence of mammographic screening that 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.

Rapid diagnosis needs to be linked to effective cancer treatment that in many settings requires some level of specialized cancer care. By establishing centralized services in a cancer facility or hospital, using breast cancer as a model, treatment for breast cancer may be optimized while improving management of other cancers.

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¹ Age-standardization is a technique used to allow populations to be compared when the age profiles of the populations are quite different.

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