Pathophysiology of breast cancer

Cancer is a process in which normal cells go through stages that eventually change them to abnormal cells that multiply out of control. Breast cancer is a malignant growth that begins in the tissue of breast. It is most common cancer in women, but it can also appear in men. As per the W.H.O. survey 5, 19,000 deaths happen around the world per year. In 2008, Breast cancer incidence was estimated that 1.38 million folks suffered with breast cancer throughout the world. In 2008, it was estimated that nearly 3, 32,000 in Europe and 1,82,460 in US were registered with new cases. The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in females. One in twenty two women in India is likely to suffer from breast cancer during their lifetime, but this figure is more in developed countries like America and UK (one in eight being victim). In 2005, International Association of Cancer Research survey showed that there will be 2,50,000 of breast cancer patients that will be seen in India by 2015, A net 3% increase per year (80 new cases per 1,00,000 population per year).

PATHOPHYSIOLOGY OF BREAST CANCER:

Breast cancers arise from a sequence that begins with an increase in the number of breast cells to the emergence of atypical breast cells followed by carcinoma in situ and finally invasive cancer. Breast cancer occurs due to interaction between the environment and a defective gene. When cells became cancerous they lost ability to stop dividing, to attach to other cells and to stay where they belong. Some mutations can cause cancer such as p-53, BRCA1 and BRCA2. These mutations are either inherited or acquired after birth. Other mutations also cause breast cancer which is deterring the P13K/AKT pathway; these are helpful in ‘apoptosis’ so that the pathway is stuck in the on position and cancer cells do not commit suicide.

Breast cancers are many types which are mainly invasive (infiltrating) breast cancer, non-invasive(ductal, lobular), estrogen fueled, inflammatory and metastatic breast cancer, in these types ductal carcinoma and invasive breast cancers are more common types accounting for about 15% and 80% respectively.

CLINICAL SYMPTOMS:

Lump or swelling in the armpit.

Changes in breast size or shape.

Dimpling or puckering of the skin – thickening and dimpling skin is sometimes called orange peel.

Inverted nipple – nipple turns inwards.

Crusting or scaling on the nipple.

THERAPEUTIC APPROACHES FOR BREAST CANCER:

In the present era we have different approaches are there to reduce the breast cancer effect in patients. The treatment of breast cancer is merely dependent on stages of breast cancer, prognosis and risk of recurrence. It is usually treated with breast conserving surgery and then may be with radiation or chemotherapy or both. In case of hormone positive cancers are treated with hormone therapy. Surgery is usually the first line of attack against breast cancer and depends on many factors. Lumpectomy, Mastectomy, lymph node removal and breast reconstruction are comes under the surgery. Chemotherapy treatment uses medicine to weaken and destroy cancer cells in the body, including cells at the original cancer site and any cancer cells that may have spread to another part of the body. It is used to treat early stage invasive breast cancer and advanced stage breast cancer, in some cases chemotherapy is give before surgery to shrink the cancer. In many cases a combination of two or more medicines will be used as chemotherapy treatment for breast cancer. Hormone therapy medicine treats either by lowering the amount of the hormone estrogen in the body or by blocking the action of estrogen on breast cancer cells. Hormonal therapy medicines can also be used to reduce the growth of advanced stage or metastic hormone receptor positive breast cancers and early stage hormone receptor positive breast cancers. Hormonal therapy medicines are not effective against hormone receptor negative breast cancers.

RISK FACTORS FOR BREAST CANCER:

Many factors can influence a woman’s getting breast cancer but having one or more risk factors does not necessarily mean that a women will get breast cancer. It is important to remember that breast cancer can also occur in women who have no identifiable risk factors. There are many risk factors are responsible for breast cancer, these are classified into three categories

Strong risk factors

Moderate risk factors

Other risk factors

Strong risk factors

AGE: The primary risk factor for breast cancer in most women is older age. Overall, 85 percent of cases occur in women 50 years of age and older, while only 5 percent of breast cancers develop in women younger than age 40.

Family history: Women who have a family history of breast cancer are at a higher risk for breast cancer than those who do not have such a history. Mainly two autosomal dominant genes, BRCA1 and BRCA2 are responsible for breast cancer.

Previous breast cancer: If women had breast cancer in one of the breast previously then there is more possibility of developing cancer in the other breast. This is basically due to hereditary mutation of BRCA gene

Moderate risk factors

Mammographic density: Women whose mammograms showing many dense areas of tissue in the breast have higher risk of acquiring breast cancer than women showing only fat tissue in her mammogram.

Biopsy abnormalities: Women whose previous breast biopsy result showed abnormal proliferation like excessive growth of glandular tissue have an increased tendency of acquiring breast cancer than non proliferative benign breast conditions like fibrocystic changes.

Radiation: For the treatment of other cancers a women who have received high doses of radiation therapy on the chest are more prevalence to breast cancer than women who have not exposed to radiation.

Other risk factors

Hormones: Throughout a women’s life breast tissue remain sensitive to hormonal changes that includes during each menstrual cycle, pregnancy and lactation. Increased exposure of estrogen is more porn to breast cancer in women because estrogen stimulates glandular proliferation in breast.

Pregnancy and breast feeding: Women who gives child birth at or after the age of 30 have double the chances and women who never given birth have triple the chances of getting breast cancers.

Hormone replacement therapy: women aging 50 to 79 who undergo hormone replacement therapy, a combination of estorogen and progesterone for approximately 5 years have increased risk of breast cancer development.

Alchol: A women who drink alcohol of two units per day have 8% chances of developing breast cancer than women consuming one unit per day. Increased alcohol consumption increases estrogen levels causing breast cancer.

Miscellaneous factors:

It may include women of high socio economic status, women working in night shifts exposing to light, race or different ethnic groups like black women and women who smoke have increased tendency of acquiring breast cancer. Women who have other diagnosed cancers of endometrium, ovary or colon have increased chances of getting breast cancer.

DIAGNOSTIC TOOLS FOR BREAST CANCER:

Evaluation of breast complaints and screening for breast cancer accounts for a significant part of primary care. These screening techniques are useful in determining the possibility of cancer. Generally triple test is used to diagnose the breast cancer; it means clinical breast examination, mammography and fine needle aspiration cytology. Other techniques for evaluation of breast cancer are ultrasonopgraphy, core needle biopsy and genetic tests to evaluate the BRCA mutagenic genes.

There are many biomarkers are there to evaluate the breast cancer most of them are useful for early detection some are useful to assess the prognosis of the disease. Risk biomarkers are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, and inherited germ line abnormalities. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers give evidence regarding response to therapy.

Mammography:

It is performed to evaluate the breast lumps or as a screening tool. It is usually recommended as part of the evaluation in women older than 35 years who have a breast mass to help evaluate the mass and to search for other lesions. Mammographic findings propose cancer include increased density, irregular border, speculation, and clustered irregular microcalcification. There have been eight major trials of mammography screening. The observed change in breast cancer mortality has varied widely among these studies but the difference is only in randomization techniques, quality of mammograms, and duration of follow-up and evolving treatments during the trial.

To assess the Mammographic density is allied with risk of breast cancer and portrays the effects of different reading conditions on the detection of changes in mammographic features. The subjects were recruited from who were participated in NBSS(National Breast Screening Study) program. The trial was randomized into two groups and subjects were allocated based on age, menopause conditions. i.e. one group contains who had undergone menopause after entry (n=202) and called it as prepostmenopausal group and another group contains who had not (n=202), called it as premenopausal group. By using a computer assisted method they obtained memmogram in each individual. Through the one year they collected mammographs in four reading methods of randomization. They assessed mammographic measures of total, dense and non-dense areas, percent density and associated variance to evaluate the mean effect of the menopause. The result of trial shows mehod-1 gave the largest mean period difference; method-4 gave the least mean period among the four mammographic measures. Finally the result shows that mammographic density is the most reliable and sensitive method for the detection of changes.

There is variation in the composition of tissue and also radiographic properties of fat, stroma and epithelium in the breasts of the radiographic appearance from one woman to the other. Literature studies have shown more density of breast is associated with increased breast cancers. Wolfe explained the relativity between variation of mammographic density and the risk of breast cancer. Women have four to six times higher risk of getting breast cancer with more than 75% of density. An extended mammographic density may make difficult to detect breast cancer by mammography. During screen tests it will increase the risk of development of cancer. The reason for the study was to relate mammographic density in base line mammogram and the increased development of breast cancer. The NBSS conducted a screening test with mammography and physical examination. The SMPBC with mammography and OBSP with mammography and physical examination. A cause control study in which the subjects who had histologically verified breast cancer were included and subjects whose diagnose of the breast cancer with less than 12 months were excluded. Through radiologist and computer assisted method the mammographic density was examined. The image of unaffected breast of case patient with image of control subjects were examined in a multiviewer in a set of 100 images. The statistical result showed that women with 10% of mammogram density had lesser risk of developing breast cancer than women with 75% of density. Increased risk of breast cancer persisted for minimum of 8 years either detected by screening or other methods. It was less in older women than in younger. 26% breast cancer and 50% of cancers detected in less than 12 months after negative screening test in women younger than age of 56. The study concluded increased risk of breast cancer is seen with higher mammographic density detected by screening or between screening tests.

CONCLUSION:

The incidence of breast cancer is rising in every country of the world especially in developing countries such as India. This is because more and more women in India are beginning to work outside their homes, food habbits, life styles and shorter duration of breast feeding and late age at first childbirth. Early detection of breast cancer has possibility to save the lives. We’ve different biomarkers to detect breast cancer. Mammography is not generally useful in women younger than 35 years who present with a lump. It is performed as an adjunct to the physical examination in evaluating as a screening tool in breast cancer. Mammography is not sufficient to exclude cancer in the evaluation of a palpable mass. Ultrasonography is very useful for evaluating breast lumps and in further defining mammographic abnormalities. It is especially useful in women younger than 35 years.