breast carcinoma, cancer of breast, mammary cancer
Breast cancer is the most common type of cancer among women (Pic. 1). Around one in eight women in the general population is expected to develop the disease at some point in her life. The majority of cases occur in women aged 50 and over. Male breast cancer is an uncommon disease accounting for only 1% of all breast cancers. It's not clear what causes breast cancer. A number of inherited mutated genes that can increase the likelihood of breast cancer have been identified (such as gene 1 (BRCA1) or gene 2 (BRCA2)). Many males with breast cancer have inherited a BRCA mutation (a mutation in either of the BRCA1 and BRCA2 genes), but there are other causes, including alcohol abuse and exposure to certain hormones and ionizing radiation.
There are significant differences between male and female breast cancer. Lesions are easier to find in males due to the smaller breast size; however, lack of awareness may postpone seeking medical attention.
Deleterious inflammation is a primary feature of breast cancer. Accumulating evidence demonstrates that macrophages, the most abundant leukocyte population in mammary tumors, have a critical role at each stage of cancer progression.
Breast cancers are classified by several grading systems. Description of a breast cancer optimally includes all of these factors.
Histopathology - Breast cancer is usually classified primarily by its histological appearance. Most breast cancers are derived from the epithelium lining the ducts or lobules, and these cancers are classified as ductal or lobular carcinoma. Carcinoma in situ is growth of low grade cancerous or precancerous cells within a particular tissue compartment such as the mammary duct without invasion of the surrounding tissue. In contrast, invasive carcinoma does not confine itself to the initial tissue compartment.
Grade - Grading compares the appearance of the breast cancer cells to the appearance of normal breast tissue. Normal cells in an organ like the breast become differentiated, meaning that they take on specific shapes and forms that reflect their function as part of that organ. Cancerous cells lose that differentiation. In cancer, the cells that would normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade) as the cells progressively lose the features seen in normal breast cells. Poorly differentiated cancers (the ones whose tissue is least like normal breast tissue) have a worse prognosis.
Stage - Breast cancer staging using the TNM system is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.
The main stages are:
Diagnosis of breast cancer used mammography, biopsy and ultrasound testing. Prognosis and survival rates vary greatly depending on cancer type, staging and treatment, and geographical location of the patient. Prognostically favorable are smaller tumor size and absence or paucity of local lymph node involvement. At a young age Diagnosis of breast cancer is associated with a higher likelihood of developing hereditary breast and ovarian cancer (HBOC). The diagnosis is made later in males—at age 67 on average—than in females with their average at 63.
Associated diseases
Complications
Complications of breast cancer can include spread of the cancer to other organs, progressive function loss of various organs. Other complications include depression, loss of sexual interest, mastalgia (breast pain), Lymphoedema (excess lymph collects in tissues) and nipple discharge.
Risk factors
The primary risk factors for breast cancer are being female, age, lack of childbearing or breastfeeding. Pregnancy causes extensive changes to the breasts, making breast cells less likely to multiply, and also less likely to develop tumours—which could explain the protective effect of pregnancy for younger women. However, it is unclear why becoming a first-time mother at an older age has the opposite effect. After age 35, breast tissue is more likely to have accumulated cells carrying cancer-causing mutations, or clusters of abnormal cells with the potential to become cancerous.
Higher hormone levels, race, economic status, dietary iodine deficiency, obesity, lack of physical exercise and drinking alcohol are other risk factors for developing breast cancer.
Smoking tobacco may increase the risk of breast cancer, with starting early and smoking more increasing the risk. Other risk factors include demographic and medical risk factors, a personal or family history of breast cancer, and atypical breast changes.
The association between breast cancer and infertility has not been consistently studied, but it may be explained by hormonal disorders linked to infertility (such as thyroid disorders or diabetes), a different reproductive risk factor profile in infertile women (such as smoking), or by a combination of these two factors.
Future fertility is a significant concern for patients undergoing cancer treatment. The adverse effects of chemotherapy and radiotherapy on female and male reproduction have long been recognized. Part of the difficulty in counseling patients regarding the risk of infertility and/or subsequent pregnancy complications is that the risks are dependent on several factors. These risks include the dose and duration of treatment, other risk factors for infertility, the age of the patient, and the patient’s baseline ovarian reserve (the ability of a woman's ovaries to produce high-quality eggs) at the time of initiation of treatment.
Somme female patients choose to have mature eggs extracted and fertilized outside of the body with sperm from a partner or donor. The resulting embryo is then frozen until the woman is in remission from disease. When the woman is ready to initiate pregnancy, the embryo is thawed and implanted into the uterus for maturation and birth. While this option is the most common fertility preservation method in women, it is not available to pre-pubescent girls, who do not have mature eggs that can be fertilized. Women who do not have a partner will need to use donor sperm.
Infertility appears to increase itself the incidence of breast carcinoma, while the potential additional risk associated with the use of fertility drugs is still debated. Hormonal treatment may be associated with hot flashes, decreased libido, depression and impotence in male.
Breast cancer patients have the lowest pregnancy rate among cancer survivors, with an overall 67 % reduction in the chance of having babies after cancer treatment as compared to the general population. However, it is not clear yet the ideal interval to wait between the end of anticancer treatments and conception. Two main interval issues should be considered: to wait until the patient is at lower risk of relapse, and to wait until the anticancer therapy is out of a patient’s system (i.e. up to 3–6 months following the last administered dose). According to expert opinion, the timing should be “personalized” taking into account age and ovarian reserve of the patient, previous treatments and time of their completion, and individual risk of relapse
Early detection is the most important factor for breast cancer. Mammography and ultrasound are currently the technique of choice for assessing breast cancer. The sensitivity of mammography varies and is affected by the density of the breast. High breast density has been strongly associated with increased risk of breast cancer.
People with genetic risk for breast cancer may consider the surgical removal of their ovaries as a preventative measure. This is often done after completion of childbearing years. This reduces the chances of developing both breast cancer (by around 50%).
Women may reduce their risk of breast cancer by maintaining a healthy weight, drinking less alcohol, being physically active and breastfeeding their children.
The selective estrogen receptor modulators (such as tamoxifen) reduce the risk of breast cancer but increase the risk of thromboembolism and endometrial cancer. There is no overall change in the risk of death. They are thus not recommended for the prevention of breast cancer in women at average risk but may be offered for those at high risk. The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.
The first noticeable symptom of breast cancer is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer cases are discovered when the woman feels a lump.
Other warning signs include:
Some patients with metastatic breast cancer opt to try alternative therapies such as vitamin therapy, homeopathic treatments, a macrobiotic diet, chiropractic or acupuncture. There is no evidence that any of these therapies are effective; they may be harmful, either because patients pass up effective conventional therapies such as chemotherapy or anti-estrogen therapy in favor of alternative treatments, or because the treatments themselves are harmful (as in the case of apricot-pit therapy — which exposes the patient to cyanide — or in chiropractic, which can be dangerous to patients with cancer metastatic to the spinal bones or spinal cord. A macrobiotic diet is neither effective nor safe as it could hypothetically induce weight loss due to severe dietary restriction.
Pharmacotherapy
Chemotherapy
Chemotherapy (drug treatment for cancer) may be used before surgery, after surgery, or instead of surgery for those cases in which surgery is considered unsuitable. The chemotherapy medications are administered in combinations, usually for periods of 3–6 months.
Chemotherapy drugs used to treat are for example:
Hormone blocking therapy
Some breast cancers require estrogen (the primary female sex hormone) 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, or alternatively block the production of estrogen with an aromatase inhibitor, e.g. anastrozole or letrozole. The use of tamoxifen is recommended for 10 years. Letrozole is recommended for 5 years. Aromatase inhibitors are only suitable for women after menopause.
Radiotherapy
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. Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given at the time of operation on the breast cancer. Radiation can reduce the risk of recurrence by 50–66%.
Surgical therapy
Depending on the staging and type of the tumor, just a lumpectomy (removal of the lump only) may be all that is necessary, or removal of larger amounts of breast tissue may be necessary. Surgical removal of the entire breast is called mastectomy (Pic. 6).
Standard practice requires the surgeon to establish that the tissue removed in the operation has margins clear of cancer, indicating that the cancer has been completely excised. If the removed tissue does not have clear margins, further operations to remove more tissue may be necessary. This may sometimes require removal of part of the pectoralis major muscle, which is the main muscle of the anterior chest wall.
Assisted reproductive technology (ART) is the technology used to achieve pregnancy in procedures such as fertility medication, artificial insemination, in vitro fertilization and surrogacy. It is reproductive technology used primarily for infertility treatments, and is also known as fertility treatment. It mainly belongs to the field of reproductive endocrinology and infertility, and may also include intracytoplasmic sperm injection (ICSI) and cryopreservation.
In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. Controlled ovarian stimulation (COS) takes around 10 days.
Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer-free interval or mortality rates in these women.
Chemotherapy and radiotherapy are toxic for oocytes, leaving few, if any, viable eggs. Egg and oocyte freezing offers women with cancer the chance to preserve their eggs so that they can have children in the future.
Embryo cryopreservation
Embryo banking has several advantages for patients interested in preserving fertility. It provides reassurance to a patient that she will have some potential to conceive if the cancer treatments result in permanent amenorrhea. There is also over 20 years of outcome data for cryopreserved embryos showing no effect on miscarriage, implantation rates, or live birth. A disadvantage of embryo banking is the need to administer ovarian stimulation medications to obtain oocytes for fertilization. Ovarian stimulation is a particular concern for patients with hormonal sensitive tumors such as breast cancer.
Oocyte cryopreservation
Human oocyte cryopreservation (egg freezing) is a process in which a woman’s eggs (oocytes) are extracted, frozen and stored. Later, when she is ready to become pregnant, the eggs can be thawed, fertilized, and transferred to the uterus as embryos. Recent advances in oocyte cryopreservation technology have expanded the use of this technology for fertility preservation. Disadvantages are similar to those of embryo banking including the risk of ovarian stimulation for patients with hormonally responsive cancers and the potential delay in starting cancer treatments. Oocyte banking is preferable over embryo banking for patients that do not have a partner and/or are not interested in utilizing donor sperm or have ethical concerns regarding cryopreservation of embryos.
Sperm cryopreservation
Because of the high probability of an indefinite period of infertility following chemotherapy, sperm cryopreservation should be recommended for all young patients with cancer prior to the start of chemotherapy. Although treatment and survival represent the primary goals of the clinical approach towards breast cancer patients, the quality of life after treatment, including the possibility of becoming fathers, requires consideration. In addition, sperm cryopreservation is another hope that encourages young patients with cancer during and after treatment.
The set of symptoms that result from two or more X chromosome in males.
Cancer that arises from the endometrium, the lining of the uterus.
Process by which a woman donates eggs for purposes of assisted reproduction or biomedical research.
A micromanipulative fertilization technique in which a single sperm is injected directly into an egg.
The procedure in which a man (sperm donor) provides his sperm for fertility treatment.
A process in which an egg is fertilised by sperm outside the body: in vitro. Own or donated gametes may be used.
