Breast Cancer Overview PDF

Breast Cancer Disease summary ○ Breast cancer is a very common and aggressive growth of transformed cells that originates in the breast ○ It has the potential to invade surrounding tissues, spread to distant sites in the body, deprive healthy tissu...

Breast Cancer Disease summary ○ Breast cancer is a very common and aggressive growth of transformed cells that originates in the breast ○ It has the potential to invade surrounding tissues, spread to distant sites in the body, deprive healthy tissue oxygen and nutrients, cause significant organ damage and ultimately, kill the patient ○ Furthermore, BC is not just one disease ○ Numerous subtypes of BC have been identified: Subtypes tend to vary in behavior and carry a different prognosis (i.e., probability for recovery) ○ Breast cancer generally arises from the epithelial lining cells of the large or intermediate sized milk ducts of the breast (i.e., ductal carcinomas) or from epithelial cells of the terminal milk ducts of the lobules (i.e., lobular carcinomas) ○ Most breast cancers (80-90%) arise from: The intermediate-sized milk ducts of the breast and are invasive (i.e., infiltrating ductal carcinoma, IDC) Most subtypes of BC are merely types of IDC with different growth patters. Infiltrating lobular carcinomas (ILC), the second most common type of BC, account for another 6-8% of all BC Paget’s disease of the nipple is a rare form of breast cancer characterized by the presence of intraepidermal tumor cells The main presenting symptoms eczema or ulceration of the nipple The most aggressive form of breast cancer, inflammatory carcinoma, constitutes 3% of all cases Inflammatory breast cancer can easily be confused with a breast infection (Mastitis), which is a much more common cause of breast redness and swelling. ○ However, among women aged 40-50 years, african american women have a higher incidence of BC than do Caucasian women ○ The lifetime risks for New Mexican Hispanics and New mexican american indians are 1 in 21 and 1 in 40, respectively ○ Over the past 50 years, the number of women diagnosed with BC has increased every year ○ The overall frequency of the disease in the United STates has been gradually increasing at the rate of.5% each year from 1987-2001, but now appears to be leveling off at approximately 11 cases per 10,000 women ○ Breast cancer causing mutations in several BC susceptibility genes account for approximately 5-10% of all cases of breast cancer and up to 80% of all BC in women younger than 50 years old ○ Two BC susceptibility genes: BRCA1 on chromosome 17 and BRCA2 on chromosome 13– account for most inherited forms of BC ○ Other gene mutations and genetic syndromes that have been linked to breast cancer include the following:  PTEN mutation (Cowden disease) STKII/LKB1 mutation (Peutz-Jeghers syndrome) ATM mutation (ataxia telangiectasia) MSH2/MLH2 mutation (Muir-Torre syndrome) CHEK-2 mutation (cell-cycle checkpoint kinase 2 defect) ○ Furthermore, a 2005 study published in the international Journal of cancer revealed that exposure to secondhand smoke also increases the risk for BC in premenopausal women ○ The california environmental protection agency had made a similar observation 1 year earlier ○ A large study of women ages 35-64 years and published in the June 2002 edition of the New England Journal of Medicine concluded that current or former use of oral contraceptives did not significantly increase the risk for BC ○ Although there are conflicting data, most research studies, including the highly reputable women’s contraceptive reproductive experience conducted 1994-1998– have not revealed an increased risk of BC from use of oral contraceptives ○ Females treated with ionizing radiation to the upper body before 30 years of age– and especially as a child or young adults– have a significantly higher incidence of BC than do females no exposed to radiation ○ Furthermore, women who consume more than one alcoholic drink per day have a slightly greater risk for developing breast cancer ○ Finally, high breast tissue density (a mammographic measure that is defined by “significantly more glandular than fatty tissue in the breast”) is also a risk factor Pathophysiology ○ Cancer of the breast, like all cancers, results from a stepwise accumulation of genetic errors in the body’s basic unit of life – the cell ○ Normally, the body maintains a system of checks and balances on cell growth so that when cells divide to produce new cells only when needed (e.g., when cells get old or injured and die) ○ Disruption of this system of check and balances on cell growth by repeated exposures to cancer-promoting agents results in uncontrolled division and proliferation of cells that eventually forms a mass known as a tumor ○ As cells continue to divide, they undergo a genetic transformation that both alters their appearance and permits them to spread to nearby lymph nodes or through the bloodstream and lymphatic vessels to other organs ○ As cancer cells spread and continue to divide, they deprive normal healthy cells of oxygen and vital nutrients and cause widespread tissue damage ○ Spread through the vertebral veins can cause new growth of cancer cells in the vertebrae, pelvic bones, ribs and skull ○ The primary mechanism by which breast cancer causes complications and death is by dissemination of cancer cells to more distant body sites – most commonly, the lungs, liver and bone ○ Metastasis (i.e., spread and growth of cancer cells at a site distant from their origin) is associated with an extremely poor outcome  ○ As described above, a woman’s age when her first child is born affects her risk for developing breast cancer– the younger she is the lower the risk ○ The most widely accepted explanation for this phenomenon is that differentiation (i.e., maturation) of the breast is completed at the end of the first term pregnancy or, if a term pregnancy has not occurred, at menopause. ○ BC can be divided into 3 distinct groups based on its link to a genetic cause: 1. Sporadic BC in which women with the disease have no family history of BC 2. Inherited cancer gene syndromes in which the mutated gene is passed to future generations by autosomal dominant transmission 3. Polygenic BC in which there is a positive family history but the cancer is not passed on to future generations with a high rate of transmission by a dominant gene ○ The total number of genes in the polygenic model, the nature of interactions among these genes, and the nature of gene interactions with environmental influences has not be determined Diagnosis: clinical manifestations and laboratory tests ○ Evaluation for BC begins with a thorough inquiry of the patient regarding symptoms, general history, and risk factors and is followed by physical examination, imaging studies and ultimately, biopsy ○ This approach naturally leads itself to a gradually increasing degree of invasiveness so that, when a diagnosis is established, the evaluation process can be terminated with minimal discomfort to the patient ○ Since more invasive investigations also tend to be the most expensive, this approach is usually the most economical ○ Technical procedures most commonly used in the diagnosis of BC include: Mammography Ultrasonography Fine-needle aspiration Computerized stereotactic guided core needle biopsy Excisional biopsy ○ Abnormal variations in breast size and contour, nipple retraction, and swelling, redness, or retraction of the skin can be identified ○ Asymmetry of the breast and retraction or dimpling of the skin can often be accentuated when the patient raises her arms overhead or presses her hands on her hips to contract the pectoralis muscles ○ With the patient sitting, axillary and supraclavicular areas are thoroughly palpated for enlarged nodes ○ Firm or hard nodes larger than 1 cm are typical of metastasis ○ Axillary nodes that are non-mobile and swelling of the ipsilateral arm indicate advanced disease ○ Firm or hard nodules of any size just above or below the clavicle also suggest metastatic disease ○ Palpation of the breast for lumps is best performed with the patient both seated and supine with the arms abducted.  Birad’s assessment: ○ 0 (incomplete)= your mammogram or ultrasound didn’t give the radiologist enough information to make a clear diagnosis; follow-up imaging is necessary ○ 1 (Negative) = there is nothing to comment on; routine screening is recommended ○ 2(Benign)= a definite benign finding; routine screening is recommended ○ 3 (probably benign)= findings have a high probability of being benign, or noncancerous (>98%); six-month follow up is recommended ○ 4 (suspicious abnormality) = finding is not characteristic of breast cancer, but there is a possibility of malignancy, or cancer (3-94%); biopsy should be considered ○ 5 (highly suspicious of malignant lesion)= (>=95%) is detected; take appropriate action as recommended by your healthcare provider ○ 6(known biopsy proven malignancy) = lesions known to be malignant are being imaged prior to definitive treatment; assure that treatment is completed Although research data have brought into question the value of mammography, the united states preventive services task force issued guidelines in 2002 concluding that there was sufficient evidence to justify recommending a mammogram every 1–2 years in women older than 40 years of age. ○ MRI scans are more sensitive than mammograms ○ However, MRI scans are also more likely to show spots in the breast that are not cancerous, can lead to a high number of avoidable biopsies, and may cause unnecessary fear and anxiety in patients. ○ That is why MRI is not recommended for women with an average risk for BC. ○ The new guideline recommends MRI screening in addition to mammograms for women who meet at least one of the following criteria: 1. They have a BRCA1 or BRCA2 mutation 2. They have a first-degree relative (i.e., parent, sibling, or child) with a BRCA1 or BRCA2 mutation 3. Their lifetime risk for BC is 20% or greater, based on one of several accepted risk assessment tools 4. They had radiation to the chest between 10 and 30 years of age 5. They have been diagnosed with a genetic syndrome that carries a high risk for BC (e.g., Cowden syndrome) ○ T0, no evidence of primary tumor ○ T1, tumor 2 cm in size ○ T2, tumor 2–5 cm in size ○ T3, tumor 5 cm in size ○ T4, tumor of any size with extension into chest wall or skin ○ N0, no regional lymph node metastasis ○ N1, metastasis to movable ipsilateral axillary lymph node(s) N2, metastasis in fixed ipsilateral axillary lymph nodes or ipsilateral internal mammary nodes ○ N3, metastasis in ipsilateral infraclavicular lymph nodes or ipsilateral internal mammary lymph nodes axillary lymph node metastasis or metastasis in ipsilateral supraclavicular lymph nodes ○ M0, no distant metastasis ○ M1, distant metastasis