It’s a typical Sunday morning at 9:00 AM with the smell of coffee brewing, the sound of footsteps running through the house and the damp feeling of crisp dew in the air as you step outside for a morning refresher. It’s sunny and 65 degrees but the wind chill forces your hands underneath your armpits to keep them warm and there it is: a tiny lump pressed against the inside of your fingertips. After multiple self-breast exams and over a thousand different scenarios running through your mind, you schedule the next available appointment with your primary care physician. As you patiently wait in the office with a notepad of all the questions you want to ask, your name is called by a friendly nurse who escorts you back to an exam room. Your doctor comes in with a smile and gently checks both of your breasts and lymph nodes in your armpits, feeling for any lumps or abnormalities. Following a confirmation that there is in fact a lump, you’re immediately scheduled for a mammogram and breast ultrasound. Next thing you know, after these procedures, in addition to a biopsy and breast MRI, your doctor enters that same exam room weeks later with papers and brochures tightly clenched between their arm and torso. With a sympathetic touch of their hand on yours and a sad look in their eyes, there’s a sudden feeling as if your stomach has relocated into each of your ten toes and the room has gone black. The only two words that stand out from the whole conversation are “Breast cancer.”
What exactly is breast cancer? Breast cancer begins when cells in the breast rapidly grow out of control, usually forming a tumor that is large enough to see on an x-ray or felt as a lump. Although breast cancer occurs almost entirely in the woman population, this does not rule men out of developing this condition. Unfortunately, there’s no universal answer to how and where this cancer starts; however, both men and women develop breasts from the same embryonal tissue. The only difference is female sex hormones, primarily estrogen, promote breast development in women and does not occur in men. Breast cancer can start from various parts of the breast and it’s important to know that not all types of breast cancer form a palpable lump. Most begin in the milk ducts, along with some that begin in the glands that produce breast milk. Other types start in further parts of the breast, which are usually classified as sarcomas or lymphomas and not typically considered as cancer of the breast.
Who is at risk of breast cancer? Breast cancer is the most common cancer among women aside from skin cancer in the United States and more common in Caucasian and Jewish decent. Approximately 1 out of 8 women will develop breast cancer at some time in their lives and it only occur in 1% of males. It is diagnosed later and tends to be more histologically aggressive in African American women. The left breast is usually larger and contains more breast tissue than the right breast, which might explain why breast cancer is more common in the left breast. Women over the age of 65 are a higher risk of developing this condition. Lung cancer is the most common cause of death in women, with breast cancer following right behind as the 2nd most common cause of death in women. According to the American Cancer Society back in 2016, the cancer death rate for men and women combined has decreased 27% from its peak in 1991 and breast cancer has decreased 40% from 1989 to 2016. The American Cancer Society’s Cancer Facts and Figures 2019 estimates 271,270 new cases and 42,260 estimated deaths between both male and female.
What risk factors will make a woman more prone to developing breast cancer? Some manners of causation for the onset of breast cancer include but are not limited to obesity, high fat diet, oral birth control pills, nulliparous, having your first child over the age of thirty-five, early menarche, late menopause, hormone replacement therapy for estrogen and previous radiation exposure. Genetic predispositions are especially high in first degree relatives and associated conditions include but are not limited to Li-Fraumeni Syndrome, Cowden’s Syndrome, mutations in the BRCA1 and BRCA2 tumor suppressant genes and mutations in HER2/neu proto-oncogenes.
How is breast cancer detected? The most common presenting symptom for breast cancer is a painless, mobile lump or mass and other symptoms include but are not limited to scaly itching breasts, breast tenderness or pain, an ulceration through the skin, satellite skin nodules on the breast, skin dimpling or puckering, nipple retraction, nipple discharge that is not breastmilk and a fixation of a mass to the skin, muscle or chest wall. A mammogram is the most sensitive and specific test for detecting breast cancer and is the only reliable method of finding a breast cancer before a palpable mass arises, which is a tumor over two centimeters in diameter. Mammography by itself detects between 40-50% of breast cancer but mammography and self-examination put together detects between 85-90%. A bilateral mammogram is required for comparison of both breasts. Ultrasound is the best diagnostic tool to differentiate between a solid or cystic breast tumor because cysts cannot be distinguished from solid tumors by a self-examination alone. MRI detects distinct histologic, biochemical and physiologic characteristics of breast cancer and therefore, is the best diagnostic tool to differentiate between normal breast tissue and malignant disease. Bone scans are helpful to detect bone metastasis and chest x-rays are helpful to detect lung metastasis.
The location of breast cancer can be determined using two methods: Quadrants and Clock Face. The frequency in the upper outer quadrant is 48%, areola is 17%, upper inner quadrant is 15%, lower outer quadrant is 11% and the lower inner quadrant is 6%. Using the quadrant method, breast cancer is usually centric in which the tumor is in only one quadrant, multicentric in which the tumor is in more than one quadrant and accounts for 3% of breast cancers, or multifocal in which more than one tumor is in different areas within the same quadrant.
Is the biopsy of a breast tumor required? The answer is yes – a biopsy is the only way to definitively diagnose cancer. Non-palpable masses require image-guided needle localization, where as palpable masses can be biopsied via fine-needle aspiration, core needle or excisional biopsy. An image-guided needle localization requires the use of an imaging technique, such as ultrasound, to obtain a small sample of cells from a suspicious area in the breast. Fine-needle aspiration uses a thoroughly small needle to extract fluids or cells from an abnormal area and a core needle biopsy uses a large and hollow needle to remove one sample of breast tissue per insertion. The most common type of excisional biopsy is a wide local excision, which is the surgical removal of a tumor or mass along with a surrounding margin of normal tissues and generally leaves behind a small, thin scar. Furthermore, a sentinel node biopsy may be performed to evaluate any lymph node involvement by injecting a radioactive substance or blue dye near the tumor to locate the sentinel node. It is then removed and examined to determine whether cancer cells are present or not present.
What does it mean by ER+/-, PR+/- and HER2/neu+/-?
When cancer arises from the epithelial tissue, it is known as carcinoma. When cancer is classified as a stage 0, has not yet invaded surrounding tissues/organs, still resembles the cell group they ascended from and there is no penetration of the basement membrane of the tissue, it is identified as “in situ.” Breast cancer can be categorized into four different classifications: Noninvasive, Invasive, Benign Dysplasia/Tumor and Sarcoma.
Ductal carcinoma in situ (DCIS) is the most common histologic type of noninvasive breast cancer, recognizable for approximately 20% and is formerly known as intraductal carcinoma. Its name is self-explanatory because this type is localized inside the ducts and has not spread into surrounding tissues. Being a very early form of breast cancer, there is generally an advantageous prognosis. DCIS can be grouped out into five histologic subtypes: Comedo, Solid, Cribform, Papillary and Micropapillary. Comedo tends to contain necrotic areas and to be more aggressive, while Papillary has both noninvasive and invasive types. The best way to detect DCIS is with a mammogram, which generally shows formed microcalcifications and a mass that is less than one centimeter and nonpalpable.
In comparison, Lobular carcinoma in situ (LCIS) is not considered to be a “true” cancer and is also known as lobular neoplasia. This type commences in the alveolar glands without invading through the walls of the lobules and is only classified at a noninvasive breast cancer because women with this condition have a 20-25% higher risk of developing an invasive breast cancer in either the same breast or opposite breast. Harder to detect with a mammogram, LCIS is accidentally detected during a biopsy for another cause most of the time. Mammograms do not show microcalcifications but does reveal masses that are usually greater than one centimeter and nonpalpable.
There are many histologic types of invasive breast cancer, which include Infiltrating Ductal Carcinoma, Infiltrating Lobular Carcinoma, Inflammatory Breast Cancer, Paget disease, Triple-Negative Breast Cancer, Medullary Carcinoma, Metaplastic Carcinoma, Mucinous Carcinoma, Tubular Carcinoma, Adenoid Cystic Carcinoma and Papillary Carcinoma. Infiltrating Ductal Carcinoma (IDC) is not only the most common histologic type of invasive breast cancer, at approximately 90%, but also is the most common histologic type of all breast cancers at 80%. Infiltrate can be defined as entering or gaining access to; therefore, IDC can be defined as a cancer that originates in the ducts of the breast and extends through the ductal walls into the surrounding adipose tissues. Likewise, Infiltrating Lobular Carcinoma (ILC) originates in the alveolar glands and extends through the lobule walls into the surrounding adipose tissues.
Inflammatory Breast Cancer (IBC) is a very rare type, only 1-3% of all breast cancers, and does not typically cause a lump, look like breast cancer or show up on a mammogram. It is usually misdiagnosed in the early stages and treated with antibiotics to begin with, such as Keflex and Clindamycin, but more testing is done after seven to ten days if symptoms worsen or do not improve. Most signs and symptoms develop rapidly, generally around three to six months and include thickening (edema/swelling) of the skin, redness involving more than one-third of the breast, retracted/inverted nipples, one breast that is larger/warmer/heavier than the other and tenderness/pain/itchiness. Peau d’ Orange, thickening and dimpling similar in the texture of an orange peel, is not caused by inflammation or infection, but by cancer cells blocking lymph vessels in the skin. IBC tends to occur in younger women, at an average age of 52 and African American women and overweight women seem to be at a higher risk. This type of invasive breast cancer is much more aggressive – it grows and spreads much more quickly than other common types. IBC is always at a locally advanced stage when it’s first diagnosed because the breast cancer cells have grown into the skin, which classifies as at least a stage IIIB. In about 1 out of every 3 cases, IBC has already metastasized to distant parts of the body, which makes it extremely difficult to treat successfully.
Paget disease is also a very rare type, at 1% of all breast cancers. It is almost always associated with DCIS and IDC because it originates in the ducts and spreads to both the skin of the nipple and the areola. The nipple and areola may appear crusted, scaly and red with areas that bleed, or ooze and the woman may notice some burning or itching. Treatment often requires a mastectomy and is DCIS is found after mastectomy procedure, the prognosis is excellent.
Triple-Negative breast cancer is also self-explanatory and arises when cells lack the estrogen receptors (ER), progesterone receptors (PR) and do not have an abundance of the HER2/neu protein on their surfaces. It tends to occur more often in younger women and African American women. This type of invasive breast cancer tends to grow and spread quickly and neither hormone therapy or immunotherapy are effective against treating successfully because of their lack in the three receptors.
Medullary Carcinoma is a very rare type, at 3-5% of all breast cancers. Some details that distinguish this away from the other types of breast cancer is that is it well-circumscribed, which means it has well-defined boundaries between tumor tissue and normal tissue. It correspondingly has a large size of the cancer cell, there is a presence of immune system cells around the edges of the tumor and it is infrequently present with lymph node involvement. The prognosis is normally better compared to the more common types on invasive breast cancer.
Metaplastic and Mucinous Carcinoma are also rare histologic types of breast cancer. Metaplastic carcinoma is formerly known as Carcinoma with Metaplasia, which includes cells that are normally not found in the breast, such as cells that may look like squamous cells or osteoblasts. Mucinous carcinoma is formally known as Colloid Carcinoma and are formed by mucus-producing cancer cells. It is more common in older women and it tends to have a better prognosis than the more common types of invasive breast cancer.
Tubular Carcinoma is a rare histologic type of invasive breast cancer as well, accounting for 2% of all breast cancers. It has a non-aggressive growth pattern and gets its name due to the way the cells are arranged when examined underneath a microscope. Approximately 10% is present with lymph node involvement.
Adenoid Cystic Carcinoma is a rare histologic type of invasive breast cancer and accounts for less than 1% of all breast cancers. It is composed of both glandular (adenoid) and cylinder-like (cystic) features when examined underneath a microscope. It tends to have a very good prognosis due to that it rarely spreads to the lymph nodes and surrounding areas.
Papillary Carcinoma is also a rare histologic type of invasive breast cancer and accounts for 1-2% of all breast cancers. It is the only breast cancer that has two different histologic subtypes: noninvasive and invasive. Noninvasive Papillary Carcinoma is a histologic subtype of DCIS and is more common than Invasive Papillary Carcinoma. The cells of these cancers are generally arranged in small, finger-like projections when examined underneath a microscope. It is more common in older women.
Cystosarcoma is a type of benign dysplasia/tumor that is usually large and encapsulated, usually benign but can be malignant and develops in the connective tissue (stroma) of the breast, where as carcinomas develop in the ducts or lobules. It primarily has a slow growth pattern that is followed by a sudden, rapid increase in size.
Mastitis is most common in women who are breastfeeding. Fibrocystic Breast Disease is most common in women over thirty years of age, who are still menstruating. They may be solitary or multiple and are generally tender and likely to regress between menstrual cycles. Fibroadenoma is the most common benign tumor of the breast and is most common in teenage girls and women in their early 20s. Cysts are benign non-solid tumors that appear as sacs containing fluid and are most common in women between the ages of forty and fifty. Both fibroadenomas and cysts present as a single encapsulated mass, are round with smooth borders and are frequently mobile.
Breast Sarcomas, also known as Angiosarcoma, is a form of cancer that starts from the cells that line the blood vessels or lymph vessels. It’s very rare to have an occurrence of this type of cancer in the breasts but when it does happen, it is usually due to as a complication of previous breast irradiation five to ten years after irradiation. This type of cancer grows and spreads quickly and can also occur in the arm of women who developed lymphedema after lymph node surgery or radiation therapy to the breast tissues.
Resources/References
- American Cancer Society. Cancer Facts & Figures 2019. Atlanta: American Cancer Society; 2019. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf
- Bolick, Diana. Cancer Management in Radiation Oncology, RADT 4621 Spring 2018.
