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Breast cancer survival - therapeutic advances but global disparities in access and outcomes.

Last month was breast cancer awareness month. As we reflected on the remarkable achievements that have been made to tackle this disease, I could not help but think about how different breast cancer is globally. Between the 1980s and 2020 the age standardize breast cancer mortality in high income countries dropped by 40%, reflecting an annual reduction in breast cancer mortality of 2-4% per year. This is remarkable progress reflecting what can be achieved when women, communities, science, and governments come together and target resources effectively.

The breast is anatomically arranged like the petals of a flower, with each petal representing the lobe and within the lobes are lobules. The lobes and lobules are linked by ducts. Breast cancer arises in the cells lining the ducts (85%) or the lobules (15%) of the breast tissue. Breast cancer often presents as a painless lump, but can also present with changes in the size or appearance of a breast, the skin, or nipple. Most breast lumps are not cancer. However, lumps that look unusual or persist for a month may be concerning and should be evaluated by a medical practitioner. Some environmental risk factors such as increasing age, alcohol use, obesity, history of radiation exposure, early onset of menstruation, delayed age of first pregnancy or use of post-menopausal hormonal therapy have been identified. Genetic mutations in genes such as BRCA1, BRCA2 and PALB-2 are associated with increased risk. But about half of women who develop breast cancer have no known risk factors.

Breast cancer has been known since ancient times and surgical management has been the approach for centuries. Early Greek surgeons provided guidance on excision and recommended leaving a wide margin, a practice that influences contemporary approaches to surgical excision of tumors. In the Middle Ages in Europe, surgery was seen as barbaric and a preference for faith healing emerged that continued until Islamic physicians revived Greek surgical practice. They also introduced the use of caustic pastes to reduce the tumors, an approach would become an early ancestor of adjuvant chemotherapy.

By the mid-18th century as understanding of anatomy had vastly improved and anesthesia, disinfection, and sterile technique were introduced surgery once again played a vital role in the treatment of breast cancer. The prevailing practice became the removal of the tumor as well as the dissection of the draining lymph nodes in the armpit. This approach lasted well into the 20th century as important surgeons such as William Halstead made the procedure the gold standard for treatment. It became known as the radical mastectomy. Observations that younger women often had more aggressive disease and that removal of the ovaries could lead to a reduction in tumor size resulted in a coupling of the radical mastectomy with the removal of ovaries. Desexing women often at any cost became a common practice. These approaches improved survival but were associated with disfigurement, pain, and complications from lymph node removal. In those that had their ovaries prematurely removed this also led to increased risk of cardiovascular, neurological, and metabolic complications.

In the 1970s and 80s Bernard Fisher, an American surgeon, generated data demonstrating that a radical mastectomy could be replaced by simpler breast conserving surgery and radiation or chemotherapy. By the mid-1990s in the US <10% of women underwent a radical mastectomy. However, the practice still continues at higher rates in less developed countries. Surgical practice in well resourced settings is largely focused on minimal surgery with breast conservation and reconstruction and removal of select ‘sentinel’ lymph nodes preventing some of the physical and emotional complications associated with earlier surgical approaches.

Understanding the role of hormones in breast cancer led to advances in hormonal therapy. Breast cancers that express hormonal receptors such as the Estrogen (ER) or progesterone receptors (PR) may be amenable to therapy with either Tamoxifen or aromatase inhibitors. Tamoxifen is an oral selective estrogen receptor modulator (SERM) used to treat breast cancer in pre and post menopausal women with ER positive breast cancer and used for breast cancer risk reduction in certain high risk women. Tamoxifen mimics estrogen in some tissues and has anti estrogen effects in others. In the breast tissue it has anti estrogen and anti-tumor effects. Defining the role of enzymes such as aromatase in the synthesis of sex hormones and the discovery of aromatase inhibitors has also had an impact on the management of breast cancer in post menopausal women.

The discovery of the cell surface receptor HER2 and the development of HER2 targeting therapies has also broadened the therapeutic toolbox. Over expression of HER2 has been identified in 20 to 30% of human breast cancers, some ovarian and gastric cancers. Breast cancers with over expression of HER2 tend to be more aggressive, have low expression of hormone receptors (ER and PR), and metastasize to the central nervous system. Monoclonal antibody therapies have been developed that target HER2.

In addition to surgery, and hormonal therapy, chemotherapy and radiation therapy play an important role in the management of breast cancer. However as the science advanced it was not coupled with improved access particularly in the developing world. Although incidence of breast cancer appears to be higher in Europe than in Africa or in white women than black women in America, outcomes and mortality are worse for black women. Black women present with breast cancer at younger ages, and often with advanced disease.

Enhancing education about breast cancer in our communities is critical to enable earlier detection. However many of the advances in disease management, therapeutic approaches and the accompanying diagnostic tests are not accessible to women in low income countries. For many in the developing world, management of breast cancer has not dramatically changed in the last few decades. As we advocate for universal access to healthcare and health systems strengthening cancer care should be a priority. Cancer and cancer mortality are often hidden from view but present high disease burden and cost in resource poor settings. According to the WHO in 2020, 2.3 million women were diagnosed with breast cancer and there were 685,000 deaths. Advocating for enhanced awareness and improved access to cancer care and treatment is critical to enable the same dramatic improvements in survival observed in breast cancer in high income countries to be experienced in the rest of the world.

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