Breast cancer – causes, symptoms, diagnosis, treatment, pathology

Breast cancer – causes, symptoms, diagnosis, treatment, pathology


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Try it free today! 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, and 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, and 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, runs 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, cannot 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 like 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. LCIS got its name many
years ago, before it was realized that it’s not a breast cancer, in the sense that it
doesn’t invade surrounding tissues. Just like healthy alveolar cells, some breast
cancer cells have hormone receptors that allow them to grow in the presence of the hormones.
Based on the type of hormone receptors, breast cancers can be divided into three major types—
estrogen receptor, or ER-positive and HER2-negative carcinoma, which is most common; HER2-positive
and ER-positive/negative carcinoma; and ER-negative and HER2-negative carcinoma. Breast cancer can cause a few complications.
First, the tumor causes local inflammation, which causes damage to the suspensory ligaments
and lactiferous ducts, resulting in their fibrosis. Next, the cancer can invade nearby
tissues like, the pectoral muscles below and the skin above. Cancer cells can also enter
and block the thin lymphatic vessels, which causes lymph to build up in the interstitial
space. Normally, this fluid build up would cause a swelling, but the attachment of suspensory
ligaments doesn’t allow the skin to stretch. So, the skin becomes thickened and dimpled,
like an orange peel, called peau d’orange appearance. Finally, tumor cells can spread
via the blood to the spine, brain and bone, or the lymph to other sites like axillary
lymph nodes and the other breast. In males, breast tissue is very thin, which makes it
easier for the cancer to spread to underlying tissues. The first symptom of breast cancer is a hard
painless lump or swelling, which is most commonly in the upper and outer part of the breast.
Additionally, there may be a swelling under the armpit, if cancer has spread to the axillary
lymph nodes. The breast becomes immobile and fixed, or stuck onto the chest wall due to
infiltration if cancer cells spread into the pectoral muscles. Another symptom is dimpling
of the skin over the breast due to involvement of skin. Fibrosis of lactiferous ducts and
suspensory ligament causes retraction, or pulling in of the nipples. When Paget disease
is present, it can cause itching, redness, crusting and discharge from the nipple. Diagnosis of breast cancer usually begins
by feeling a breast lump. Breast cancer can be treated effectively when its detected early
in the course of the disease. That’s why regular screening with mammography, which
is an Xray of the breasts, is done in high-risk individuals. In addition, imaging using ultrasound
and MRI may be done to detect the tumor. Finally, a biopsy of the swelling, or a fine needle
aspiration and cytology, where fluid from the swelling is taken, may be done to confirm
the diagnosis. To determine the risk of breast cancer, each
one is staged by the TNM system. ‘T’ indicates the size of the tumor and whether or not it
has grown in nearby areas, for example, the chest wall muscles. ‘N’ describes the
degree to which the cancer has spread to nearby lymph nodes, particularly the axillary lymph
nodes. And finally ‘M’ indicates the degree to which the cancer has spread to other sites
or metastasized. Each of these categories is ranked from 0–4 with four being the most
severe. Finally, the combinations of these sub-stages determine the stage group, which
are assigned 0 to IV. Treatment for breast cancer is based on the
type and stage of the cancer, but commonly involves surgery, radiation therapy, chemotherapy,
and hormonal therapy. Localized tumors are removed surgically by partial mastectomy,
where the affected part is removed, and larger tumors which have spread to nearby tissue
are removed by total mastectomy, where the entire breast is removed. In addition, nearby
structures like lymph nodes may also be removed if the cancer has metastasized to them. Hormone
therapy is used when tumor cells have hormone receptors like estrogen and HER2, and may
include medications which block the formation or effects of estrogen. Alright, as a quick recap… breast cancer,
or breast carcinoma is the uncontrolled growth of epithelial cells lining the ducts and lobules
of breast. Breast cancer usually begins as an in-situ carcinoma, which can either be
ductal carcinoma in-situ, or DCIS, which is localized to the ducts, or lobular carcinoma
in-situ, or LCIS, which is localized within the lobules. Over time, in-situ carcinoma
can invade the basement membrane to become invasive carcinoma involving the ducts and
lobules. Breast cancer screening by mammography is done for early detection of cancer, which
can be treated by a variety of treatment options, which include surgery, radiation therapy,
chemotherapy, and hormonal therapy.