41 Breast Cancer

Breast Cancer – What is it?

Breast cancers can arise from several different tissue types within the breast, though mostly commonly originate in either ductal or lobular cells.  Ductal epithelial cells line the lactation ducts and lobules are made of glandular epithelial cells that produce milk during lactation.  Approximately 29,000 Canadians are diagnosed with breast cancer annually.  It is predicted that 1 in 8 females in Canada will be diagnosed with breast cancer at some point in their lives.

Breast Cancer – Risk Factors and Prevention Strategies

Ductal carcinoma is the most common form of breast cancer, and more often occurs in biological females (XX), with biological males (XY) accounting for less than 1% of all cases.  The incidence rate amongst intersex individuals or those with differences of sexual development is not well documented, though individuals with Klinefelter Syndrome (XXY) are known to have an increased risk of developing breast cancer.  In general, the risk associated with biological sex is due to the exposure levels of the breast cells to estrogen and progesterone.

Another risk factor is age, with the incidence rate being the highest between 50-69 years of age.  Family history, particularly within first-degree relatives is a risk factor due to inherited genetic susceptibilities that affect hormone levels as well as breast density.  Inheriting either BRCA1 or BRCA2 genetic variations (e.g., mutations) can increase one’s risk as both genes are tumor suppressor genes (TSGs), which are required for ensuring appropriate regulation of cell cycling, cell cycle arrest, exiting of the cell cycle and differentiation or senescence.  BRCA1 or BRCA2 mutations are rare occurring in 1 in 500 people, though it is carried more commonly in those of Ashkenazi Jewish descent, of whom approximately 1 in 40 females have inherited a BRCA mutation.

Risk factors for developing breast cancer include longer exposure levels to estrogen due to early menarche (before 12yrs old), late menopause (after 55yrs old), nulliparity (never been pregnant) or hormone replacement therapy (HRT) for longer than 5yrs.  Interestingly, early full-term pregnancy (before the age of 30) reduces the risk of breast cancer further in comparison with later first full-term pregnancies.  Tall adult height is thought to be a pre-disposing factor due to levels of or duration of exposure to growth and puberty hormones.  Unlike with ovarian cancer, birth control pills that contain both estrogen and progesterone are thought to increase the risk of developing breast cancer.  Sedentary behaviour, obesity, alcohol consumption, high-fat diet, low intake of vegetables as well as night-shift work are considered risk factors.  As well, exposure to carcinogens (e.g., smoking, x-rays, pollutants) and immunosuppression are risk factors for all cancers.

Prevention strategies include: healthy diet following Canada’s Food Guide, healthy lifestyle following the Canadian Physical Activity Guidelines.  Other prevention strategies include limiting one’s exposure to alcohol, tobacco products, ionizing radiation and other known carcinogens.  Vaccinations and precautions against infections with oncoviruses (e.g., HPV, HBV, HCV, EBV) including viruses that can be immunosuppressive (e.g., HIV) is recommended in preventing cancers that can harm in primary organs and then by metastasizing.

Some individuals that have a family history may choose to have DNA tests performed to determine whether they carry BRCA1 or BRCA2 mutations and therefore have an increased risk of developing breast cancer.  Biological females that have BRCA1 or BRCA2 mutations have a 85% chance of developing breast cancer in their lifetime, and more often in both breasts.  For biological males, BRCA1 mutations increase the risk of breast cancer slightly (1-5%) and BRCA2 mutations increase the risk of cancer to 5-10%.

Hereditary Breast and Ovarian Cancer (HBOC) is inherited in an autosomal dominant manner, meaning that if just one of the two copies of either BRCA1 or BRCA2 is mutated, there is an increased risk of both breast and ovarian cancers.  Females with BRCA1 or BRCA2 mutations may choose to have their fallopian tubes and ovaries removed (bilateral salpingo-oophorectomy) in addition to prophylactic (preventative) mastectomy.

Breast Cancer – Signs & Symptoms

Monthly self-examinations are recommended to ensure early detection.  New painless or painful lumps, discharge, dimpling, sores should be reported immediately to a physician and examined further.  50% of cases develop in upper outer quadrant of breast, so being sure to cover this area during self-exams is recommended.  Most tumors occur unilateral and earlier onset is more aggressive

Late signs and symptoms of breast cancer can include loss of appetite, unexplained weight loss, nausea, jaundice, bone pain, headache, and dyspnea.  The clinical manifestations are due to the manner in which the cancer spreads through lymph to lungs, brain, bone, and liver.

Breast Cancer – Diagnosis

Mammogram screening is often recommended every 1-2 years, especially after the age of 40, if there is a history of breast cancer within first-degree relatives.  Mammograms utilize low-dose x-rays and assist with detecting breast cancers when they are at small, early, more treatable stages.  Breast cancer can metastasize when the tumor size is small (1-2cm) and can spread quickly to axillary (armpit) lymph nodes and then to secondary organs. 

If breast cancer is suspected, often imaging is performed (e.g., mammography, ultrasound) and a biopsy (guided by imaging) is performed to analyze cells for morphological changes that indicate dysplasia or anaplasia.  Often thin needles are used to perform biopsies to ensure the procedure is minimally invasive.  Biopsy and microscopic analysis of cells is the only definitive way to diagnose breast cancer.  Cell that have been biopsied are also examined to determine whether the cancerous cells are expressing estrogen and progesterone hormone receptors.  If so, this can mean the anti-estrogen treatments may be chosen.

If the cancer has spread, lymph node biopsies are performed.  Biopsies typically start in the sentinel lymph node as it is the first lymph node through which lymph fluid from the area of the tumor enters.  If cancerous cells are found in the sentinel lymph nodes, other lymph nodes will be examined to determine the extent of the spread.  If spread is suspected in the bones or other areas of the body further imaging may be performed (e.g., bone scans/x-rays, MRI).  At times blood tests are performed to determine the levels of serum tumor markers (e.g., cancer antigen 15-3 (CA15-3, carcinoembryonic antigen (CEA)) that can be present with breast cancer and indicate the state of metastasis.

Breast Cancer – Treatment

Treatment often depends on the stage of breast cancer as well as whether the individual is post-menopause.  Treatments can include:  surgery (e.g., lumpectomy, mastectomy, oophorectomy), chemotherapy (e.g., anti-mitotic drugs), radiation therapy, hormone therapy (e.g., anti-estrogen, oophorectomy) and targeted therapy (e.g., cancer enzyme inhibitors).

At times, complications arise from lymph radiation or lymphadenectomy resulting in impaired lymph drainage of the arm, leading to swelling and stiffness in the arm.  Often this is treated with physiotherapy exercises and drainage strategies (e.g., compression bandaging, lymph vessel grafting, supermicrosurgical lymphaticovenous anastomosis).

Think about questions:

1.  Why is oophorectomy considered hormone therapy?
2. Why is oophorectomy only helpful in treating breast cancer in females that are pre-menopausal?