USMLE® Step 1 style questions USMLE
A 50-year-old woman comes for a follow-up meeting after she was diagnosed with invasive ductal carcinoma breast cancer. A 2-cm spiculated lesion was seen on mammography and confirmed with biopsy. She would like to know what the prognosis is for her condition. Which of the following findings is the worse prognostic factor for her conditions?
Content Reviewers:Rishi Desai, MD, MPH, Yifan Xiao, MD
Contributors:Sam Gillespie, BSc, Jahnavi Narayanan, MBBS, Robyn Hughes, MScBMC, Kaia Chessen, MScBMC
Breast cancer, or breast carcinoma, is an uncontrolled growth of epithelial cells within the breast. It’s the second most common cancer in women, but can also, on rare occasion, affect men as well.
Breast cancer is also the second leading cause of cancer deaths in women after lung cancer. This is largely due to the fact that oftentimes breast cancers don’t cause any pain or discomfort until they’ve spread to nearby tissues.
The breasts are milk-producing glands that sit on the chest wall, on either side of the breast-bone. They lie on top of the ribs and the pectoral muscles, and they’re divided into three main parts.
The glandular tissue that makes the milk, is made up of 15 to 20 lobules. Inside each of these lie a bunch of grape-like structures called the alveoli, which are modified sweat glands surrounded by a basement membrane made largely of collagen.
Zooming in on the alveoli, there’s a layer of alveolar cells that secrete breast milk into the lumen which is the space in the center of the gland.
Wrapping around the alveolus are special myoepithelial cells that squeeze down and push the milk out of the lumen of the alveolus, down the lactiferous ducts, and out one of the pores on the nipple.
Now, surrounding the glandular tissue is the stroma, which contains adipose or fat tissue, and this makes up the majority of the breast.
Suspensory ligaments called Cooperʼs ligaments, run through the stroma and help keep it in place. These ligaments attach to the inner surface of the breast skin on one end and the pectoralis muscles on the other.
Just below the skin over the breast, there’s a network of tiny lymphatic vessels that drain the lymph, which is a fluid containing cellular waste products and white blood cells. These lymphatic vessels mainly drain into a group of lymph nodes in the axilla, or the armpit.
Now, the cells of glandular tissue have receptors for certain hormones like, estrogen and progesterone, which are released by the ovaries, and prolactin which is released by the pituitary gland.
These hormones stimulate the alveolar cells to divide and increase in number, which makes the lobule enlarge.
Without these hormones, the glandular cells, particularly the alveolar cells, can’t survive, and undergo apoptosis which is programmed cell death.
For example, after menopause, estrogen production stops, which leads to death of the alveolar cells. And, over time, that breast tissue gets replaced by fat.
During the menstrual cycle, there’s increased secretion of estrogen and progesterone from the ovaries, and right after menstruation, that secretion decreases.
As a result, during every menstrual cycle, the alveolar cells undergo division and apoptosis.
Men have some breast tissue as well, but they lack milk secreting alveoli. Each time cells divide there’s a chance that a genetic mutation will occur and a mutation can lead to tumor formation.
So with more menstrual cycles, thereʼs in increased risk of tumor formation. That’s why there’s an increased risk of breast cancer with things that increase the number of menstrual cycles - like early age of menarche, which is the first menstrual bleeding, and late age of menopause.
Similarly, medications containing estrogen also increase the risk of breast cancer.
There are also other environmental risk factors such as ionizing radiation, like from chest X-rays and CT scans.
On the flip side, some things that are associated with a decreased risk of breast cancer include early pregnancy and a longer time breastfeeding.
Breast cancer has also been linked to specific mutations in tumor suppressor genes, such as Breast Cancer gene, or BRCA-1 and BRCA-2, and TP53, which normally slow down cell division or make cells die if they divide uncontrollably.
Mutations in BRCA-1 or BRCA-2 are both autosomal dominant mutations, which can be inherited and cause familial breast cancer. In addition to breast cancer, they also cause an increased risk of ovarian cancer.
Some breast cancers also have mutations in the ERBB2 gene that increase human epidermal growth factor receptor 2, or HER-2, which when activated, promotes the growth of cells.
In males, breast cancer is usually caused by inherited mutations in the BRCA-1 and 2 genes.
Once a cancer-causing mutation does occur, the affected cell, which is most commonly an epithelial cell that lines the ducts or the lobules, begins to grow and replicate out of control, forming a tumor.
This tumor, also called in-situ carcinoma, is initially localized within the basement membrane of the alveoli, and can be of two types.
The first type is called ductal carcinoma in-situ, or DCIS, and that’s where tumor cells grow from the wall of the ducts, into the lumen.
If left untreated DCIS over time can cross the basement membrane to become invasive ductal carcinoma.
Also, cancer cells from DCIS can migrate along the lactiferous duct and through the pore, onto the skin over the nipple. This is called Paget disease of the nipple.
These cancer cells release a substance called mobility factor, which helps them break into and settle in between the squamous epithelial cells.
As the cancer cells move into the epithelium, there’s inflammation which brings extracellular fluid out through breaks in the skin. This fluid then dries and forms crusts over the skin surface.
The second type is called lobular carcinoma in-situ, or LCIS, and that’s where clusters of tumor cells grow within the lobules, without invading the ducts, causing the affected alveoli to enlarge.
Unlike DCIS, over time LCIS doesn’t cross the basement membrane to form invasive lobular carcinoma.
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
- "Mammographic Density and the Risk and Detection of Breast Cancer" New England Journal of Medicine (2007)
- "Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy" The Lancet (2012)