Breast Cancer Etiology And Pathophysiology Pdf
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- Breast cancer
- What Are the Risk Factors for Breast Cancer?
- What to know about breast cancer
Studies have shown that your risk for breast cancer is due to a combination of factors. The main factors that influence your risk include being a woman and getting older. Most breast cancers are found in women who are 50 years old or older.
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Crit Rev Oncol Hematol. Aging: Risk increases with advancing age. Risk at age 40 is and risk at age 80 is Height : Taller women, both pre- and postmenopausal, have a slightly increased risk; likely correlated with hormonal stimulation. Arch Intern Med. Weight : High body-mass index BMI is a risk factor for post menopausal women, likely due to adipose tissue production of estrogen via aromatase. High BMI may lower risk for premenopausal breast cancer due to anovulation see Polycystic ovarian syndrome chapter and reduction of circulating estrogen and progesterone.
History of benign proliferative breast disease : Previous breast biopsy showing proliferative changes, particularly with atypical epithelial cells. Proliferation of breast epithelium occurs in the luteal phase of the ovulatory cycle, thereby increasing risk of promotion of initiated cells see Carcinogenesis chapter.
Breast gene expression changes permanently after pregnancy, increasing DNA repair pathways and control over apoptosis. However, pregnancy itself causes a transient risk of breast cancer because of increased estrogen and progesterone exposure, which promotes proliferation in initiated cells.
Late age at first full-term birth increases time for exposure to carcinogens. J Mammary Gland Biol Neoplasia. Nat Rev Cancer. Hormone replacement therapy HRT : Combined estrogen and progesterone therapy has been linked to the development of breast cancer in postmenopausal women; not estrogen alone. Oral contraceptives OCP do not increase risk.
Estrogen and progesterone in HRT likely promotes preneoplastic lesions rather than initiate them. Since OCP is used in younger women, the number of preneoplastic lesions is much lower than in postmenopausal women, rendering the OCP risk much lower.
Nat Rev Clin Oncol. Ionizing radiation : Breast tissue is sensitive to carcinogenic effects of radiation. Risk is highest in the developing breast and absent after menopause.
See Carcinogenesis chapter for mechanism of ionizing radiation. Breast Cancer Res. Smoking : First hand smoking at a young age as well as before a first full term pregnancy.
Smoking allows tobacco carcinogens to initiate breast cells prior hormonal stimulation during young adulthood and pregnancy.
Cigarette smoke contains at least 20 carcinogens that are known to transform breast cells. Tob Control. Alcohol : Alcohol has been shown to increase the amount of circulating estrogen, possibly by decreasing hepatic metabolism, increasing aromatase activity, or increasing adrenal sex hormone production. Hematol Oncol Clin North Am. Affected first-degree relatives: Risk increases with number of affected relatives, especially with early-onset breast cancer, bilateral breast cancer or male breast cancer.
See below for details. Li-Fraumeni syndrome: Characterized by early onset breast cancers, sarcomas, brain tumours, adrenal cortical tumours and acute leukemias. Cowden syndrome: Characterized by high rate of breast cancer and mucocutaneous findings, thyroid disorders and endometrial carcinomas. BRCA1 gene is located on chromosome 17q21 and is classified as a tumour suppressor gene. It functions as a pleiotropic DNA damage repair protein.
BRCA2 gene is located on chromosome 13q12 and also classified as a tumour suppressor gene; though shares no homology with the BRCA1 gene. BRCA2 protein functions as a mediator of the core mechanism of homologous recombination. Its mutations are linked to breast carcinomas that are ER and PR positive. Though rarely associated with basal-like phenotype but still linked to a higher grade II or III when compared to age-matched sporadic cases.
When estrogen enters the cell, it binds the ER and the complex migrates into the nucleus and leads to the production of transcription proteins that induces changes in the cell. Two major hypotheses attempt to explain the tumorigenic effects of estrogen: i genotoxic effects of estrogen metabolites via generation of radicals initiator and ii the hormonal properties of estrogen inducing proliferation of cancers as well as the premalignant cells promoter.
HER2 belongs to the epidermal growth factor receptor EGFR family of proto-oncogenes and currently is not known to have a ligand. However, the protein has been shown to form clusters within the cell membranes in malignant breast tumours. Its mechanism of carcinogenesis remains largely unknown, but overexpression is associated with rapid tumour growth, shortened survival, increased risk of recurrence after surgery, and poor response to conventional chemotherapeutic agents.
Very few clinical signs and symptoms exist for breast cancer raising the importance of screening tests in diagnosis. Breast mass — a dominant mass is a distinct mass that is asymmetric with the other breast.
Benign findings are often associated with cysts, fibroadenomas, or fibrocystic changes. Malignant disease often has abnormal cell proliferation and calcifications, manifesting as a fixed, firm mass with irregular borders. Any suspicious dominant mass should undergo diagnostic tests see below. Nipple discharge — usually benign, but discharge with blood, from a single duct, or associated with breast mass raises probability of cancer. Cyclic mastalgia : Hormonal changes during the menstrual cycle trigger an increase in breast size and volume.
Your feedback has been received. Our editorial team will review your comments in the next few days. We appreciate your feedback! Thank you, Sultan Chaudhry and Eric Wong. Overview Definition : breast cancer refers to several types of neoplasm arising from breast tissue, the most common being adenocarcinoma of the cells lining the terminal duct lobular unit.
This chapter only discusses this adenocarcinoma type. Breast cancer is the most prevalent cancer in Canadian women , and is the second leading cause of cancer deaths in women. However, the prognosis is good if detected early.
Canadian Cancer Society Statistics Hormonal cancer : breast cancer requires a hormonal supply to develop, much like the tissue it arises out of. Risk of breast cancer increases with lifetime estrogen exposure. The majority of breast cancers are hormone sensitive, meaning that they express estrogen receptors and proliferate in response to estrogen stimulation.
Endocrine therapies that inhibit estrogen production are effective in treating hormone-sensitive breast cancer. The genes code for a DNA repair pathway that is important for protecting against mutations. The loss of either gene confers a high risk of breast cancer, as well as other cancers. Thank you Your feedback has been received. Female: Primary risk factor. Lifetime risk in females is compared to males at History of cancer: Previous history of breast, endometrial or ovarian cancer.
Absence of discrete lump Mobile Soft Smooth borders Tender. Discrete lump Fixed Firm Irregular borders Non-tender. Milky, green or yellow Multiple duct Produced with manual expression. Bloody or serous Single duct Produced spontaneously. Bilateral Diffuse Worse during the late luteal phase of menstrual cycle Subsides with onset of menstruation.
Altered cognitive function and local neurological signs.
Crit Rev Oncol Hematol. Aging: Risk increases with advancing age. Risk at age 40 is and risk at age 80 is Height : Taller women, both pre- and postmenopausal, have a slightly increased risk; likely correlated with hormonal stimulation. Arch Intern Med.
What Are the Risk Factors for Breast Cancer?
If your institution subscribes to this resource, and you don't have a MyAccess Profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus. Please consult the latest official manual style if you have any questions regarding the format accuracy. Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast.
Not a MyNAP member yet? Register for a free account to start saving and receiving special member only perks. T he preceding chapters have summarized the available evidence for the relationship between environmental exposures and breast cancer, as well as the many challenges inherent in studying this issue.
What to know about breast cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The risk of developing certain cancers can be reduced by not smoking, maintaining a healthy weight, limiting alcohol intake, eating plenty of vegetables , fruits , and whole grains , vaccination against certain infectious diseases, limiting consumption of processed meat and red meat , and limiting exposure to direct sunlight. In , about
Breast cancer, the most frequently occurring cancer in women, is a major public health problem, with 1,, estimated new cases worldwide with nearly , related deaths. Breast cancer is highly heterogeneous in its pathological characteristics, some cases showing slow growth with excellent prognosis, while others being aggressive tumors. Current predictions and statistics suggest that both worldwide incidence of breast cancer and related mortality are on the rise. According to American Cancer Society, one in eight women in the United States will develop breast cancer in her lifetime. It has been predicted that the worldwide incidence of female breast cancer will reach approximately 3. These numbers reflect the magnitude of breast cancer incidence, its effect on society worldwide and the need for urgency for preventive and treatment measures. While technological advances in medical sciences and health care have made it possible to detect the disease early and to start the treatment early on to prevent the progress of the disease into a metastatic state, there are several unanswered questions with regard to the molecular mechanisms that underlie the aggressiveness of certain forms of this disease.
Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis is confirmed by biopsy. Treatment usually includes surgical excision, often with radiation therapy, with or without adjuvant chemotherapy, hormone therapy, or both. About , new cases of invasive breast cancer and about 42, deaths from it are expected in In addition, about 48, new cases of in situ breast cancer are expected in 2.
Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women after lung cancer. Advances in screening and treatment for breast cancer have improved survival rates dramatically since The chance of any woman dying from breast cancer is around 1 in 38 2. The ACS estimate that , women will receive a diagnosis of invasive breast cancer, and 62, people will receive a diagnosis of noninvasive cancer in In the same year, the ACS report that 41, women will die as a result of breast cancer.