Breast Cancer

Breast Cancer

Breast Cancer

 

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.

Signs and symptoms
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 women feels a lump. The earliest breast cancers are detected by a mammogram. Lumps found in lymph nodes located in the armpits can also indicate breast cancer.

Indications of breast cancer other than a lump may include thickening different from the other breast tissue, one breast becoming larger or lower, nipple changing position or shape or becoming inverted, skin puckering or dimpling, a rash on or around a nipple, discharge from nipple/s, constant pain in part of the breast or armpit, and swelling beneath the armpit or around the collar bone. Pain (“mastodynia”) is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.

Inflammatory breast cancer is a particular type of breast cancer which can pose a substantial diagnostic challenge. Symptoms may resemble a breast inflammation and may include itching, pain, swelling, nipple inversion, warmth and redness throughout the breast, as well as an orange- peel texture to the skin referred to as peau d’orange; as inflammatory breast cancer does not show as a lump there’s sometimes a delay in diagnosis.

Another reported symptom complex of breast cancer is Paget’s disease of the breast. This syndrome presents as skin changes resembling eczema, such as redness, discoloration, or mild flaking of the nipple skin. As Paget’s disease of the breast advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget’s disease of the breast also have a lump in the breast.

In rare cases, what initially appears as a fibroadenoma (hard, movable non- cancerous lump) could in fact be a phyllo des tumor? Phyllodes tumor are formed within the stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllo des tumors are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline, or malignant.

Occasionally, breast cancer presents as metastatic disease- that is, cancer that has spread beyond the original organ. The symptoms caused by metastatic breast cancer will depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult breast cancer, as can jaundice or neurological symptoms. These symptoms are called non- specific, meaning could be manifestations of any other illnesses.

Most symptoms of breast disorders, including most lumps, do not turn out to represent underlying breast cancer. Fewer than 20% of lumps, for example, are cancerous, and benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. Nevertheless, the appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.

Risk factors:

The primary risk factors for breast cancer are female sex and older age. Other potential risk factors include: genetics, lack of child bearing or lack of breast feeding, higher levels of certain hormones, certain dietary patterns, and obesity.

Lifestyle
Smoking tobacco appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk. In those who are long term smokers, the risk is increased 35% to 50%. A lack of physical activity has been linked to 10% of cases.

There is a relationship between diet and breast cancer, including an increased risk with a high fat diet, alcohol intake, and obesity, related to higher cholesterol levels. Dietary iodine deficiency may also play a role.

Other risk factors include radiation, and shift- work. A number of chemicals have also been linked including: polyclorinated biphenyls, polycyclic aromatic hydrocarbons, organic solvents and a number of pesticides. Although the radiation from mammography is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.

Genetics:
Some genetic susceptibility may play a minor role in most cases. In those with a first degree relative with the disease the risk of breast cancer between the age of 40 and 50 is double that of the general population.

Medical conditions:
Breast changes like atypical ductal hyperplasia and lobular carcinoma in situ, found in benign breast conditions such as fibrocystic breast changes, are correlated with an increased breast cancer risk. Diabetes mellitus might also increase the risk of breast cancer.

Pathophysiology:
Breast cancer, like other cancers, occurs because of an interaction between an environmental (external factor and a genetically susceptible host. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when they lose their ability to stop dividing, to attach to other cells, to stay where they belong, and to die at the proper time.

Normal cells will commit cell suicide (apoptosis) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. Sometimes, the genes along these protective pathways are mutated in a way that turns them permanently “on” rendering the cell incapable of committing suicide when it is no longer needed.

Mutations that can lead to breast cancer have been experimentally linked too estrogen exposure.

Diagnosis:
Most types of breast cancer are easy to diagnose by microscopic analysis of a sample or biopsy of the affected area of the breast.

The two most commonly used screening methods, physical examination of the breasts by a healthcare provider and mammography, can offer an approximate likelihood that a lump is cancer, and may also detect some other lesions, such as a simple cyst. When these examinations, are inconclusive, a healthcare provider can remove a sample of the fluid in the lump for microscopic analysis ( a procedure known as fine needle aspiration, or fine needle aspiration and cytology- FNAC ) to help establish the diagnosis. The needle aspiration may be performed in healthcare provider’s office or clinic using local anaesthetics if required. A finding of clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, physical examination of the breasts, mammography, and FNAC can be used to diagnose breast cancer with a good degree of accuracy.

Other options for biopsy include a core biopsy or vacuum- assisted breast biopsy, which are procedures in which a section of the breast lump is removed; or an excisional biopsy, in which the entire lump is removed. Very often the results of physical examination by a health care provider, mammography, and additional tests that may be performed in special circumstances (such as imaging by ultrasound or MRI) are sufficient to warrant excisional biopsy as the definitive diagnostic and primary treatment method.

Prevention:
Women may reduce their risk of breast cancer by maintaining a healthy weight, drinking less alcohol, being physically active and breastfeeding their children. The benefits with moderate exercise such as brisk walking are seen at all age groups including post-menopausal women. Marine omega- 3 polyunsaturated fatty acids appear to reduce the risk.

Screening:
Breast cancer screening refers to testing otherwise- healthy women for breast cancer in an attempt to achieve an earlier diagnosis under the assumption that early detection will improve outcomes. A number of screening test have been employed including: clinical and self-breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.

A clinical or self-breast exam involves feeling the breast for lumps or other abnormalities. Clinical breast exams are performed by health care providers, while self-breast exams are performed by the person themselves. Evidence does not support the effectiveness of either type of breast exam, as by the time a lump is large enough to be found it is likely to have been growing for several years and thus soon be large enough to be found without an exam. Mammographic screening for breast cancer uses x- rays to examine the breast for any uncharacteristic masses or lumps. During a screening, the breast is compressed and a technician takes photos from multiple angles. A general mammogram takes photos of the entire breast, while a diagnostic mammogram focuses on a specific lump or area of concern.

A number of national bodies recommend breast cancer screening by mammography every two years in women between the ages of 50 and 74. The reports point out that in addition to unnecessary surgery and anxiety, the risk of more frequent mammograms include a small but significant increase in breast cancer induced by radiation. Whether MRI as a screening method has greater harms or benefits when compared to standard mammography is not known.

Management:
The management of breast cancer depends on various factors, including the stage of the cancer. Increasingly aggressive treatments are employed in accordance with the poorer the patient’s prognosis and the higher the risk of recurrence of the cancer following treatment.

Breast cancer is usually treated with surgery, which may be followed by chemotherapy or radiation therapy, or both. A multidisciplinary approach is preferable. Hormone receptor- positive cancers are often treated with hormone- blocking therapy over courses of several years. Monoclonal antibodies, or other immune- modulating treatments, may be administered in certain cases of metastatic and other advanced stages of breast cancer.

Surgery
Surgery involves the physical removal of the tumor, typically along with some of the surrounding tissue. One or more lymph nodes may be biopsied during the surgery; increasingly the lymph node sampling is performed by a sentinel lymph node biopsy.

Standard surgeries include:
* Mastectomy: Removal of the whole breast
* Quadrantectomy: Removal of one quarter of the breast
* Lumpectoy: Removal of a small part of the breast.

Once the tumor has been removed, if the patient desires, breast reconstruction surgery, a type of plastic surgery, may then be performed to improve the aesthetic appearance of the treated site. Alternatively, women use breast prostheses to stimulate a breast under clothing, or choose a flat chest. Nipple/Areola prostheses can be used at any time following the mastectomy.

Medication
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. Aspirin may reduce mortality from breast cancer.

There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone- blocking agents, 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., amastrozole or letrozole. Aromatase inhibitors, however, are only suitable for post- menopausal patients. This is because the active Aromatase in post-menopausal women is different from the prevalent form in premenopausal women, and therefore, these agents are ineffective in inhibiting the predominant Aromatase of premenopausal women.

Chemotherapy
Chemotherapy is predominantly used for cases of breast cancer in stages 2-4, and is particularly beneficial in estrogen receptor- negative (ER-) disease. The chemotherapy medications are administered in combinations, usually for periods of 3-6 months. One of the most common regimens, known as “AC”, combines cyclophosphamide with doxorubicin (Adriamycin). Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as “CAT”. Another common treatment, which produces equivalent results, is cyclophosphamide, methotrexate, and fluorouracil (or “CMF”). Most chemotherapy medications work by destroying fast- growing and/or fast- replicating cancer cells, either by causing DNA damage upon replication or by other mechanisms. However, the medications also damage fast- growing normal cells, which may cause serious side effects. Damage to the heart muscle is the most dangerous complication of doxorubicin, for example.

Monoclonal antibodies
Trastuzumab ( Herceptin), a monoclonal antibody to HER2 ( a cell receptor that is especially active in some breast cancer cells), has improved the 5-year disease free survival of stage 1-3 HER2- positive breast cancers to about 87%( overall survival 95%). When stimulated by certain growth factors, HER2 causes cellular growth and division; in the absence of stimulation by the growth factor, the cell will normally stop growing. Between 25% and 30% of breast cancers overexpress the HER2 gene or its protein product, and overexpression of HER2 in breast cancer is associated with increase disease recurrence and worse prognosis. When trastuzumab binds to the HER2 in breast cancer cells that overexpress the receptor, trastuzumab prevents growth factors from being able to bind to and stimulate the receptors, effectively blocking the growth of the cancer cells. Trastuzumab, however, is very expensive and its use may cause serious side effects (approximately 2% of patients who receive it suffer significant heart damage). Further, trastuzumab is only effective in patients with HER2 amplification/overexpression.

Radiation
Radiation 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 radiation). Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given at the time of operation on the breast cancer – intraoperative. 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).

Prognosis
Prognosis is the long term outcomes of the condition. This includes the probability of progression- free survival (PFS) or disease- free survival. These predictions are based on experience with breast cancer patients with similar classification. A prognosis is an estimate, as patients with the same classification will survive a different amount of time, and classifications are not always precise. Survival is usually calculated as an average number of months (or years) that 50% of patients survive, or the percentage of patients that are alive after 1, 5, 15, and 20 years. Prognosis is important for treatment decisions because patients with a good prognosis are usually offered less invasive treatments, such as lumpectomy and radiation or hormone therapy, while patients with poor prognosis are usually offered more aggressive treatment, such as more extensive mastectomy and one or more chemotherapy drugs.

Prognostic factors:
Prognostic factors are reflected in the classification scheme for breast cancer including stage, (I.e., tumor size, location, whether disease has spread to lymph nodes and, other parts of the body), grade, recurrence of the disease, and the age and health of the patient.

The stage of the breast cancer is the most important component of traditional classification methods of, breast cancer, because it has a great effect on the prognosis than the other considerations. Staging takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the poorer the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, and skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer- free zones and close- to- normal cell behavior (grading). Size is not a factor in staging unless the cancer is invasive. For example, Ductal Carcinoma in Situ (DCIS) involving the entire breast will still be stage zero and consequently an excellent prognosis with a 10-year disease free survival of about 98%.

* stage 1 cancers (and DCIS, LCIS) have an excellent prognosis and 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.

The breast cancer grade is assessed by comparison of the breast cancer cells to normal breast cells. The closer to normal the cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4.

The presence of estrogen and progesterone receptors in the cancer cell is important in guiding treatment. Those who do not test positive for these specific receptors will not be able to respond to hormone therapy, and this can affect their chance of survival depending upon what treatment options remain, the exact type of the cancer, and how advanced the disease is.

In addition to hormone receptors, there are other cell surface proteins that may affect prognosis and treatment. HER2 status directs the course of treatment. Patients whose cancer cells are positive for HER2 have more aggressive disease and may be treated with the ” targeted therapy ” , trastuzumab ( Herceptin ), a monoclonal antibody that targets this protein and improves the prognosis significantly.

Younger women tend to have a poorer prognosis than post- menopausal women due to several factors. Their breasts may change with their menstrual cycles, they may be nursing infants, and they may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biological factors contributing to a higher risk of disease recurrence for younger women with breast cancer.

High mammographic breast density, which is a marker of increased risk of developing breast cancer, may not mean an increased risk of death among breast cancer patients.

Since breast cancer in males is usually detected at later stages, outcome are typically worse.

Psychological aspects:
The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe.

Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen- receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.

On the other hand, a small 2007 study conducted by researchers at the college of Public Health of the University of Georgia suggested a need for greater attention to promoting functioning and psychological well- being among older cancer survivors, even when they may not have obvious cancer- related medical complications. The study found that older breast cancer survivors showed multiple indications of decrements in their health- related quality of life, and lower psychosocial well- being than a comparison group. Survivors reported no more depressive symptoms or anxious mood than the comparison group, however, they did score lower in measures of positive psychosocial well- being, and reported more depressive mood and days affected by fatigue. As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.

Epidemiology:
Worldwide, breast cancer is the most common invasive cancer in women. Breast cancer comprises 22.9% of invasive cancers in women and 16% of all the female cancers.

The incidence of breast cancer varies greatly around the world; it is lowest in less developed countries and greatest in the more- developed countries.

The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles. Breast cancer is strongly related to age with only 5% of all breast cancers occurring in women under 40 years old.

Pregnancy:
Cancers found during or shortly after pregnancy appear at approximately the same rate as other cancers in women of a similar age. As a result, breast cancer is one of the more common cancers found during pregnancy, although it is still rare, because only about 1 in 1000 pregnant women experience any sort of cancer.

Diagnosing a new cancer in a pregnant women is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy. As a result, cancer is typically discovered at a somewhat later stage than average in many pregnant or recently pregnant women. Some imaging procedures, such as MRIs (magnetic resonance imaging), CT scans, ultrasounds, and mammograms with fetal shielding are considered safe during pregnancy; some others, such as PET scans are not.

Treatment is generally the same as for non- pregnant women. However, radiation is normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are, postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries to speed the start of treatment are not uncommon. Surgery is generally considered safe during pregnancy but some other treatments, especially certain chemotherapy drugs given during the first trimester, increase the risk of birth defects and pregnancy loss (spontaneous abortions and stillbirths). Elective abortions are not required and do not improve the likelihood of the mother’s surviving or being cured.

Radiation treatments may interfere with the mother’s ability to breast feed her baby because it reduces the ability of that breast to produce milk and increases the risk of mastitis. Also, when chemotherapy is being given after birth, many of the drugs pass through breast milk to the baby, which could harm the baby.

Regarding future pregnancy among breast cancer survivors, there is often fear of cancer recurrence. On the other hand, many still regard pregnancy and parenthood to represent normalcy, happiness and life fulfillment.

 

Dr. A.K.M. Aminul Hoque
Associate Prof. (Medicine)
Dhaka Medical College & Hospital,
Dhaka

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