Breast cancer is a type of cancer originating from breast tissue, most commonly from the inner lining of milk ducts or
the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas, while those
originating from lobules are known as lobular carcinomas. Breast cancer occurs in humans and other mammals. While the overwhelming
majority of human cases occur in women, male breast cancer can also occur.
The size, stage, rate of growth, and other characteristics of a breast cancer determine the kinds of treatment. Treatment may
include surgery, drugs (hormonal therapy and chemotherapy), radiation and/or immunotherapy. Surgical removal of the tumor provides
the single largest benefit, with surgery alone curing many cases. To increase the likelihood of cure, several chemotherapy regimens are
commonly given in addition to surgery. Radiation is used after breast-conserving surgery and substantially improves local relapse rates and
in many circumstances also overall survival. Some breast cancers are sensitive to hormones such as estrogen and/or progesterone, which makes
it possible to treat them by blocking the effects of these hormones.
Breast cancer is usually treated with surgery and then possibly with chemotherapy or radiation, or both. A multidisciplinary
approach is preferable. Hormone positive cancers are treated with long term hormone blocking therapy. Treatments are given with increasing
aggressiveness according to the prognosis and risk of recurrence. The NPI Nottingham Prognostic Index is a useful tool in assessing the prognosis
Stage 1 cancers (and DCIS) have an excellent prognosis and are generally treated with lumpectomy and sometimes radiation. HER2+ cancers should
be treated with the trastuzumab (Herceptin) regime. Chemotherapy is uncommon for other types of stage 1 cancers.
Stage 2 and 3 cancers with a progressively poorer prognosis and greater risk of recurrence are generally treated with surgery (lumpectomy or
mastectomy with or without lymph node removal), chemotherapy (plus trastuzumab for HER2+ cancers) and sometimes radiation (particularly
following large cancers, multiple positive nodes or lumpectomy).
Stage 4, metastatic cancer, (i.e. spread to distant sites) has poor prognosis and is managed by various combination of all treatments from
surgery, radiation, chemotherapy and targeted therapies. 10-year survival rate is 5% without treatment and 10% with optimal treatment.
Surgery involves the physical removal of the tumor, typically along with some of the surrounding tissue and frequently sentinel node biopsy.
Standard surgeries include:
Mastectomy: Removal of the whole breast.
Quadrantectomy: Removal of one quarter of the breast.
Lumpectomy: Removal of a small part of the breast.
If the patient desires, then breast reconstruction surgery, a type of cosmetic surgery, may be performed to create an aesthetic appearance.
In other cases, women use breast prostheses to simulate a breast under clothing, or choose a flat chest. Nipple/areola prostheses can be used
at any time following the mastectomy.
Drugs used after and in addition to surgery are called adjuvant therapy. Chemotherapy or other types of therapy prior to surgery are called neoadjuvant therapy.
There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone blocking therapy, chemotherapy, and monoclonal antibodies.
Hormone blocking therapy
Some breast cancers require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER+) and progesterone
receptors (PR+) on their surface (sometimes referred to together as hormone receptors). These ER+ cancers can be treated with drugs that either
block the receptors, e.g. tamoxifen (Nolvadex), or alternatively block the production of estrogen with an aromatase inhibitor, e.g. anastrozole
(Arimidex) or letrozole (Femara). Aromatase inhibitors, however, are only suitable for post-menopausal patients. This is because the active
aromatase in postmenopausal women is different from the prevalent form in premenopausal women, and therefore these agents are ineffective in
inhibiting the predominant aromatase of premenopausal women.
Predominately used for stage 2–4 disease, being particularly beneficial in estrogen receptor-negative (ER-) disease. They are given in combinations,
usually for 3–6 months. One of the most common treatments is cyclophosphamide plus doxorubicin (Adriamycin), known as AC. Most chemotherapy
medications work by destroying fast-growing and/or fast-replicating cancer cells either by causing DNA damage upon replication or other mechanisms;
these drugs also damage fast-growing normal cells where they cause serious side effects. Damage to the heart muscle is the most dangerous complication
of doxorubicin. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer
cells. Another common treatment, which produces equivalent results, is cyclophosphamide, methotrexate, and fluorouracil (CMF).
Trastuzumab (Herceptin), a monoclonal antibody to HER2, has improved the 5-year disease free survival of stage 1–3 HER2+ breast cancers to about
87% (overall survival 95%).Trastuzumab, however, is expensive, and approximately 2% of patients suffer significant heart damage. Other monoclonal
antibodies are also undergoing clinical trials. Trastuzumab is only effective in patients with HER2 amplification/overexpression.Between 25 and
thirty percent of breast cancers have an amplification of the HER2 gene or overexpression of its protein product. This receptor is normally stimulated
by a growth factor which causes the cell to divide; in the absence of the growth factor, the cell will normally stop growing. Overexpression of this
receptor in breast cancer is associated with increased disease recurrence and worse prognosis.
Radiotherapy is given after surgery to the region of the tumor bed and regional lymph nodes, to destroy microscopic tumor cells that may have escaped
surgery. It may also have a beneficial effect on tumor microenvironment. Radiation therapy can be delivered as external beam radiotherapy or as
brachytherapy (internal radiotherapy). Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given at the
time of operation on the breast cancer- intraoperatively.
The largest randomised trial to test this approach was the TAR-GIT-A Trial which found that targeted intraoperative radiotherapy was equally effective
at 4-years as the usual several weeks of whole breast external beam radiotherapy. Radiation can reduce the risk of recurrence by 50–66% (1/2 – 2/3
reduction of risk) when delivered in the correct dose and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy
or Wide local excision).