Breast Cancer A Family Medicine Perspective

Breast Cancer A Family Medicine Perspective
By Robert R. Zaid, DO PrimeCare of Novi

Overview Epidemiology Etiology Risk Factors Screening Presentation
Workup Staging Treatment

Breast Cancer Epidemiology
Etiology Risk Factors Screening Presentation Workup Staging Treatment Incidence: Invasive breast cancer 1 1.4 million new cases in 2008 Incidence rates for 2002 varied internationally 3.9 cases per 100,000 in Mozambique 101.1 cases per 100,000 in the United States Past 25 years Breast cancer incidence rates have risen globally Highest rates occurring in the westernized countries Change in reproductive patterns Increased screening Dietary changes Decreased activity Mortality Mortality has been decreasing Especially in industrialized countries. 1 American Cancer Society

Etiology Risk Factors Screening Presentation Workup Staging Treatment Projection (2009) United States Estimated 192,370 new cases in women 1,910 cases in men Incidence rates 70’s to 90’s had increasing incidence Decreased by 2.2% per year Why? Reduced use of hormone replacement therapy (HRT) Women’s Health Initiative in 2002 Swart, R; Downey, L, Breast Cancer

Etiology Risk Factors Screening Presentation Workup Staging Treatment Lifetime Risk of Breast Cancer All Women 12.7% Non-Hispanic Whites 13.3% African American Women 9.98% More likely to be diagnosed with larger, advanced stage tumors (>5 cm) Swart, R; Downey, L, Breast Cancer

Etiology Risk Factors Screening Presentation Workup Staging Treatment Death rates Steadily decreased since 1990 Estimated 40,610 breast cancer deaths for 2009 Women < 50 years Largest decrease in mortality 3.3% per year Thought to represent Earlier detection Improved treatment modalities Swart, R; Downey, L, Breast Cancer

Breast Cancer Etiology
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Mechanism- Current understanding of breast tumorigenesis Molecular alterations at the cellular level Outgrowth and spread of breast epithelial cells Immortal features Uncontrolled growth Genomic profiling Demonstrated the presence of discrete breast tumor subtypes Luminal A Luminal B Basal HER2+ The exact number of disease subtypes and molecular alterations from which these subtypes derive remains to be fully elucidated Generally align closely with the presence or absence of hormone receptor and mammary epithelial cell type (luminal or basal). Swart, R; Downey, L, Breast Cancer

Breast Cancer Etiology
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment The figure below summarizes the current general understanding of breast tumor subtypes, prevalence, and the major associated molecular alterations. This view of breast cancer, not as a set of stochastic molecular events, but as a limited set of separable diseases of distinct molecular and cellular origins, has altered thinking about breast cancer etiology, type-specific risk factors, prevention, and treatment strategies.

Breast Cancer Risk Factors
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Risk factors found by studies Many of these factors form the basis for breast cancer risk assessment tools. Common denominator Level and duration of exposure to endogenous estrogen Increase lifetime exposure to estrogen Premenopausal women Early menarche Nulliparity Late menopause Postmenopausal women Obesity and hormone replacement therapy

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Family History of breast cancer 1st degree relative Risk 5 times greater in women with 2 or more first-degree relatives A family history of ovarian cancer in a first-degree relative Especially if the disease occurred at an early age (< 50 years old) Associated with a doubling of risk of breast cancer

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Exogenous hormones Oral contraceptives (OCs) Hormone replacement therapy (HRT) 1.25 increased risk among current users of oral contraceptives Risk appears to decrease As age and time from oral contraceptive discontinuation increases Breast cancer risk returns to that of the average population after approximately 10 years following cessation of oral contraceptives

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment HRT Consistent epidemiologic data support an increased risk of breast cancer incidence and mortality (2003) with the use of postmenopausal HRT Directly associated with length of exposure Lobular (relative risk [RR]=2.25, 95% confidence interval [CI]= ) Mixed ductal–lobular (RR=2.13, 95% CI= ) Tubular cancers (RR=2.66, 95% CI= ).

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Combo estrogen plus progestin Increased risk as compared to estrogen only Not statistical significance (p=0.06) Women’s Health Initiative (WHI) Indicate that the adverse outcomes associated with long-term use outweigh the potential disease prevention benefits particularly for women older than 65 years Protective factors Late menarche Anovulation Early menopause (spontaneous or induced) Lowering endogenous estrogen levels Shortening the duration of estrogenic exposure.

Advanced age Family history Two or more relatives (mother, sister) One first-degree relativ Family history of ovarian cancer in women <50y Personal history Personal history Positive BRCA1/BRCA2 mutation Breast biopsy with atypical hyperplasia Breast biopsy with LCIS or DCIS Reproductive history Early age at menarche (<12 y) Late age of menopause Late age of first term pregnancy (>30 y)/nulliparity Use of combined estrogen/progesterone Current or recent use of oral contraceptives Lifestyle factors Adult weight gain Sedentary lifestyle Alcohol consumption >4 >5 >2 3-4 4-5 8-10 2 1.5-2 1.25 1.5 Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment

Breast Cancer Risk Assessment Tools
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Multivariate Methods for estimating breast cancer 2 types Estimate absolute risk of developing cancer Estimate likelihood that an individual is a carrier of a gene mutation BRCA1 BRCA2

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment BRCA screens BRCAPRO Identifies 50% of mutation negative families Fails to screen 10% of mutation carriers Myriad I, II Manchester Ontario Family History U.S. Preventive Services Task Force (USPSTF) Does not specifically endorse any of these genetic risk assessment models because of insufficient data to evaluate their applicability to asymptomatic, cancer-free women. USPSTF does support the use of a greater than 10% risk probability for recommending further evaluation with an experienced genetic counselor for decisions regarding genetic testing.

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Risk Prediction Models Gail Model (1989) Made from data from Breast Cancer Detection and Demonstration study Probability of developing breast cancer over a defined age interval Intended to improve screening guidelines Gail Model 2 Includes history of first-degree affected family members Used extensively in clinical practice Most accurate for non-Hispanic White women who receive annual mammograms Tends to overestimate risk in younger women who do not receive annual mammograms Reduced accuracy in populations with demographics (age, race, screening habits) that differ from the population on which it was built

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Care Address concerns regarding applicability of the Gail Model to African American women Data from a large case control study of African American CARE Model demonstrated high concordance between the numbers of breast cancer predicted and the number of breast cancers observed among African American women when validated in the WHI cohort. Improvements in risk prediction and clinical tools are likely to emerge in the next few years with the addition of such factors as breast density, mammographic density change across exams, use of HRT, and a variety of other factors such as weight, age at birth of first live child, and number of first-degree relatives with breast cancer. Going forward, it is likely that there will be models specifically for risks of premenopausal versus postmenopausal cancers and for specific breast cancer subtypes (luminal versus basal).

Breast Cancer Genetic Factors
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Heredity 5-10% of women have an identifiable familial predisposition 20-30% of women with breast cancer have a relative with history BRCA1 and BRCA2 mutations Responsible for 3-8% of all cases of breast cancer 15-20% of familial cases Gene mutation on Chromosome 17 and 18 Account for majority of inherited disease Believed to be tumor suppressor genes Rare mutations are seen in the PTEN, TP53, MLH1, MLH2, and STK11 genes.

Breast Cancer Genetic Factors
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Mutation rates may vary by ethnic and racial groups. BRCA1 mutations Highest rates occur among Ashkenazi Jewish women (8.3%) Hispanic women (3.5%) Non-Hispanic white women (2.2%) African American women (1.3%) Asian American women (0.5%) Women with BRCA1 or BRCA2 gene Estimated 50-80% lifetime risk of developing breast cancer. Specifically, BRCA1 mutations are seen in 7% of families with multiple breast cancers and 40% of families with breast and ovarian cancer. People with a BRCA1 mutation have a lifetime risk of 40% for developing ovarian cancer and are also at a higher risk of colon cancer and prostate cancer. Breast cancer that develops in BRCA1 mutation carriers are more likely to be high-grade, and ER, PR, and HER-2/neu negative (triple negative) or basal-like subtype. BRCA2 mutations are identified in 10-20% of families at high risk for breast and ovarian cancers and in only 2.7% of women with early-onset breast cancer. Women with a BRCA2 mutation have approximately 10% lifetime risk of ovarian cancer. BRCA2 mutation carriers who develop breast cancer are more likely to have a high grade, ER+/PR+, and HER-2/neu negative cancer (luminal type). BRCA2 is also a risk factor for male breast cancer. Other cancers associated with BRCA2 mutations include prostate, pancreatic, fallopian tube, bladder, non-Hodgkin lymphoma, and basal cell carcinoma. Li-Fraumeni syndrome, caused by TP53 mutations , is associated with multiple cancers, including the SBLLA syndrome (sarcoma, breast and brain tumors, leukemia, and laryngeal and lung cancer). Cancer susceptibility is transmitted in an autosomal dominant pattern, with a lifetime risk of breast cancer of 90%. Li-Fraumeni syndrome is responsible for approximately 1% of cases of familial breast cancer. Bilateral breast cancer is noted in up to 25% of patients. Cowden disease is a rare genetic syndrome caused by PTEN mutations. It is associated with intestinal hamartoma, cutaneous lesions, and thyroid cancer. The prevalence rate of breast cancer in women with this disease is approximately 30%. Benign mammary abnormalities (eg, fibroadenomas, fibrocystic lesions, ductal epithelial hyperplasia, and nipple malformations) are also common. Other rare genetic disorders, such as Peutz-Jeghers and hereditary nonpolyposis colorectal carcinoma (HNPCC), are associated with an increased risk of breast cancer.

Breast Cancer Breast Cancer Screening
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Early detection Primary defense available to patients Preventing the development of life-threatening breast cancer Breast tumors that are smaller or nonpalpable Treatable and have a more favorable prognosis Survival benefit of early detection Early detection is widely endorsed Women younger than 40 years Monthly breast self-examination practices Clinical breast exams every 3 years are recommended, beginning at age 20 years. In addition, rather than annual screening, the USPSTF guidelines recommend that screening mammography be performed biennially (Grade B recommendation). The USPSTF concludes that there is currently insufficient evidence to assess the additional benefits and harms of screening mammography in women 75 years or older and thus recommends stopping screening at age 74 years.4

Breast Cancer Breast Cancer Screening
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Mammography Annual screening mammography beginning at age 40 years Widely recommended approach in the United States U.S. Preventive Services Task Force (USPSTF) Nov 2009 Updated breast cancer screening guidelines Recommend against routine mammography before age 50 years 40 to 49 years of age USPSTF suggests that the decision to start regular screening mammography be individualized and should include the patient's values regarding specific benefits and harms American College of Obstetricians and Gynecologists (ACOG) Continues to recommend adherence to current ACOG guidelines Screening mammography every 1-2 years for women aged 40-49 Screening mammography every year for women age 50 or older ACOG notes, however, that because of the USPSTF downgrading, some insurers may no longer cover some of these studies. In addition, rather than annual screening, the USPSTF guidelines recommend that screening mammography be performed biennially (Grade B recommendation). The USPSTF concludes that there is currently insufficient evidence to assess the additional benefits and harms of screening mammography in women 75 years or older and thus recommends stopping screening at age 74 years.4

Breast Cancer Breast Self Examination
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Breast self-examination Inexpensive and noninvasive procedure Evidence supporting effectiveness Controversial and largely inferred Not been found to reduce mortality Improvements in treatment for early, localized disease Breast self-examination and clinical breast exam, continues to be recommended Clinical trials support combining clinical breast exam with mammography

Breast Cancer Breast Self Examination
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Recommendations USPSTF Inadequate evidence to make a recommendation for teaching or performing BSE 2009 USPSTF guidelines recommend against teaching women how to perform BSE Resulted in additional imaging procedures and biopsies ACOG Continues to recommend counseling BSE has potential to detect palpable breast cancer

Breast Cancer Mammography
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Mammography Demonstrated to be an effective tool Prevention of advanced breast cancer in women at average risk Best available population-based method to detect breast cancer at an early stage Often reveals a lesion before it is palpable by clinical breast examination On average 1-2 years before noted by breast self-examination 20-30% of women still do not undergo screening as indicated Physician recommendation Access to health insurance Digital Mammograpy Allows the image to be recorded and stored Computer-aided diagnosis (CAD) systems Using an image modified to improve evaluation of specific areas in question.

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Recommendations: USPSTF Estimates benefit of mammography in women 50-74 years to be a 30% reduction risk of death 40-49 years, the risk of death is decreased by 17% Non-white women and those of lower socioeconomic status remain less likely to obtain mammography services and more likely to present with life-threatening, advanced-stage disease

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Ultrasound Widely available and useful adjunct to mammography MRI Combination of T-1, T-2, and 3-D contrast-enhanced MRI techniques has been found to be highly sensitive Approximating 99% Limitations 10-fold higher cost than mammography Poor specificity (26%) Significantly more false-positive reads Significant additional diagnostic costs and procedures. While mammography remains the most cost-effective approach for breast cancer screening, the sensitivity (67.8%) and specificity (75%) are not ideal. As reported, mammography combined with clinical breast examination slightly improves sensitivity (77.4%) with a modest reduction in specificity (72%). Comparisons between recently introduced digital mammography and screen-film mammography suggest that the sensitivity of full-field digital mammography is superior to screen film mammography in certain subsets of women. For example, digital mammography demonstrates improved detection rates for younger women and for women with more dense breasts. Improved imaging modalities with greater sensitivity are of particular benefit for women at the highest risk and for women whose breast images are difficult to interpret. Generally used to assist the clinical examination of a suspicious lesion detected via mammogram or physical examination. As a screening device, the ultrasound is limited by a number of factors, but most notably by the failure to detect microcalcifications and poor specificity (34%).

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Below are the criteria for using breast MRI screening per the American Cancer Society (ACS).6 Annual breast MRI Evidence based BRCA mutation First-degree relative of BRCA carrier, but untested Lifetime risk approximately 20-25% or greater as defined by BRCAPRO or other risk models Lifetime risk of breast cancer Radiation to chest when aged years Li-Fraumeni syndrome and first-degree relatives Cowden and Bannayan-Riley-Ruvalcaba syndromes and first-degree relatives

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Insufficient evidence to recommend for or against MRI screening Lifetime risk 15-20%, as defined by BRCAPRO or other risk models Lobular carcinoma in situ or atypical lobular hyperplasia (ALH) Atypical ductal hyperplasia (ADH) Heterogeneously or extremely dense breast on mammography Women with a personal history of breast cancer, including ductal carcinoma in situ American Cancer Society does not recommend the use of breast MRI in women who have less than 15% lifetime risk

Breast Cancer Presentation
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Mammogram- Often irst detected as an abnormality on a mammogram Mammographic features Asymmetry Microcalcifications A mass Architectural distortion Larger tumors May present as a painless mass Pain 5% of patients with a malignant mass present with breast pain Other symptoms Immobility Skin changes (ie, thickening, swelling, redness) Nipple abnormalities (ie, ulceration, retraction, spontaneous bloody discharge)

Breast Cancer Workup Core biopsy Percutaneous vacuum-assisted
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Core biopsy Percutaneous vacuum-assisted Image guided breast biopsy Recommended diagnostic approach Performed with Ultrasound Stereotactic, or MRI guidance Core biopsies spare the need for operative intervention Provides pathological results quicker than surgical excisions Excisional biopsy As the initial operative approach Shown to increase the rate of positive margins Typically, patients who undergo a core needle biopsy, whether directed by imaging studies or palpation, have a titanium marker clip placed at the biopsy site. These clips are particularly helpful when planning a lumpectomy for non-palpable breast lesions that require preoperative image-guided wire-localization or for patients who undergo neoadjuvant chemotherapy, resulting in a pathological complete response.

Breast Cancer Workup Palpation directed core biopsy
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Palpation directed core biopsy If a breast mass may be palpable but not correlate with imaging Complications of a diagnostic core or excisional biopsy Hematoma Infection Scarring Re-operation Sampling error resulting in inaccurate diagnosis. Typically, patients who undergo a core needle biopsy, whether directed by imaging studies or palpation, have a titanium marker clip placed at the biopsy site. These clips are particularly helpful when planning a lumpectomy for non-palpable breast lesions that require preoperative image-guided wire-localization or for patients who undergo neoadjuvant chemotherapy, resulting in a pathological complete response.

Breast Cancer Histological Findings
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Ductal Carcinoma in situ (DCIS) Lobular Carcinoma in situ (LCIS) Medullary Carcinoma Mucinous Carcinoma Tubular Carcinoma Papillary Carcinoma Metaplastic Carcinoma Mammary Paget’s Disease Increased use of screening mammography has resulted in a dramatic increase in the detection of DCIS. Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Today, 90% of DCIS cases are

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Ductal Carcinoma in situ (DCIS) Identified in ducts (non-invasive) Identified on mammography Suspicious calcifications, Distribution Linear Clustered Segmental Focal Mixed DCIS is divided into comedo (ie, cribriform, micropapillary, solid) and noncomedo subtypes, which provides additional prognostic information regarding likelihood of progression or local recurrence Increased use of screening mammography has resulted in a dramatic increase in the detection of DCIS. Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Today, 90% of DCIS cases are

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Ductal Carcinoma in situ (DCIS) Standard treatment of DCIS is surgical resection with or without radiation Adjuvant radiation and hormonal therapies Reserved for Younger women Patients undergoing lumpectomy Comedo subtype Mastectomy 30% of women with DCIS in the United States Conservative Surgery 30% with conservative surgery alone Conservative surgery with whole breast radiation 40% with conservative surgery followed by whole-breast radiation therapy Increased use of screening mammography has resulted in a dramatic increase in the detection of DCIS. Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Today, 90% of DCIS cases are

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Ductal Carcinoma in situ (DCIS) Axillary or sentinel lymph node dissection is not routinely recommended for patients with DCIS Metastatic disease Disease to the axillary node in 10% of patients Whole-breast radiotherapy Delivered 5-6 weeks following Tamoxifen Adjuvant therapy for breast conserving surgery Only hormonal therapy currently approved Aromatase inhibitor (anastrozole) Currently in clinical trials Increased use of screening mammography has resulted in a dramatic increase in the detection of DCIS. Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Today, 90% of DCIS cases are

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Lobular Carcinoma in situ (LCIS) Found in the lobules (or glands) Non-palpable mass Diffuse distribution throughout the breast Incidence Doubled over last 25 years 2.8% per 100,000 women Peak incidence is in women aged years No consistent features on breast imaging Often an incidental finding 10-20% of women with LCIS develop invasive breast cancer Within 15 years from diagnosis. LCIS is considered a biomarker of increased breast cancer risk Treatment options Chemoprevention with a SERM Bilateral mastectomy Close observation.

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Medullary Carcinoma Relatively uncommon (5%) Invasive Occurs in younger women Presentation Bulky palpable mass with axillary lymphadenopathy Diagnosis Sheets of anaplastic tumor cells with scant stroma Moderate or marked stromal lymphoid infiltrate Histologic circumscription or a pushing border Other findings DCIS may be observed in the surrounding normal tissues ER, PR, and HER2/neu are typically negative, and TP53 is commonly mutated. Roughly 30% of patients have lymph node metastasis. Prognosis Good Recent analysis of 609 medullary breast cancer specimens from various stage I and II NSABP protocols indicate that overall survival and prognosis are not as good as previously reported.

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Mucinous Carcinoma Rare histologic type Fewer than 5% of invasive breast cancer Produces Mucin Usually presents during the seventh decade Excellent prognosis (>80% 10-year survival). Mucin production is the histologic hallmark with 2 main forms, type A and B, with AB lesions possessing features of both. Type A mucinous carcinoma represented the classic variety with larger quantities of extracellular mucin, whereas type B is a distinct variant with endocrine differentiation. DCIS is not a frequent occurrence, though it may be found. Most cases are ER and PR positive, but HER2/neu overexpression is rare. Additionally, these carcinomas predominantly express glycoproteins MUC2 and MUC6

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Tubular Carcinoma Uncommon histologic type 1-2% of all breast cancers Single layer of epithelial cells Low incidence of lymph node involvement Very high overall survival rate

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Papillary Carcinoma 1-2% of all carcinomas Usually seen in women older than 60 Types Cystic (non-invasive) Good prognosis Micropapillary ductal carcinoma (invasive) Poor prognosis Lymph node metastasis

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Metaplastic Carcinoma 1% of breast cancers Combination of adenocarcinoma plus mesenchymal and epithelial components Wide variety of histological patterns Spindle-cell carcinoma Carcinosarcoma Squamous cell carcinoma of ductal origin Adenosquamous carcinoma Carcinoma with pseudosarcomatous metaplasia Matrix-producing carcinoma Metaplastic breast cancer tumors Larger More rapidly growing Commonly node negative Typically ER, PR, and HER-2 negative Average age of onset in the sixth decade Higher incidence in African Americans.

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Metaplastic Carcinoma Demonstrated a worse prognosis for metaplastic breast cancer as compared to infiltrating ductal carcinoma 3-year overall survival rate of 48-71% 3-year disease-free survival rate of 15-60% Prognosis / predictors of poor overall survival Large tumor size Advanced stage Nodal status does not appear to impact survival in metaplastic breast cancer Surgery is used to treat up to 95% of women with metaplastic breast cancer. Few data support the effectiveness of systemic chemotherapy in patients with metaplastic breast cancer and its use has been extrapolated from the treatment of more common types of breast cancer. A review of chemotherapy and response in a series of 27 patients with metaplastic breast cancer found only one partial response with a doxorubicin-containing regimen in the setting of metastatic disease. As in soft-tissue sarcomas, metaplastic breast cancer shows a tendency for local recurrence and for hematogenous spread to lung, liver, and bone.

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Mammary Paget’s Disease 1-4% of all breast cancers Peak incidence is seen in the sixth decade of life (mean age 57 y) Adenocarcinoma Localized within the epidermis of the nipple-areola complex Paget cells Large Pale epithelial cells Presentation Lesions Unilateral developing insidiously Scaly Fissured Oozing Erythematous nipple-areola complex Retraction or ulceration of the nipple is often noted Itching, tingling, burning, or pain. Mammary Paget disease is associated with an underlying breast cancer in 75% of cases. Overall 5-year and 10-year survival rates are 59% and 44%, respectively. Standard treatment of mammary Paget disease is surgical excision (modified radical mastectomy with lymph node excision). Breast conserving surgery can achieve satisfactory results, but at the risk of local recurrence. Adjuvant chemotherapy with tamoxifen may increase survival in premenopausal patients with lymph node metastasis. Poor prognostic factors include a palpable breast tumor, lymph node involvement, histological type, and patient younger than 60 years

Breast Cancer Prognosis
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Predictors / prognostic factors of BC Axillary lymph node status Tumor size Lymphatic/vascular invasion Patient age Histologic grade Histologic subtypes (eg, tubular, colloid [mucinous], papillary) Response to neoadjuvant therapy Estrogen receptor/progesterone receptor status Her2/neu gene amplification and/or overexpression Breast cancer predictive factors include the following: Lymph node status Standard treatment of mammary Paget disease is surgical excision (modified radical mastectomy with lymph node excision). Breast conserving surgery can achieve satisfactory results, but at the risk of local recurrence. Adjuvant chemotherapy with tamoxifen may increase survival in premenopausal patients with lymph node metastasis. Poor prognostic factors include a palpable breast tumor, lymph node involvement, histological type, and patient younger than 60 years

Breast Cancer Staging T- tumor size N- Lymph node status M- Metastasis
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment T- tumor size N- Lymph node status M- Metastasis Separated into stages 0- IV Survival Rates 5 year Stages 99-100% I 95-100% II 86% III 57% IV 20%

Breast Cancer Staging National Cancer Center Network (NCCN) guideline
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment National Cancer Center Network (NCCN) guideline Stage I or II Recommends a history and physical examination Laboratory studies (CBC with differential, liver and renal function tests, and calcium levels) Stage III Chest x-ray or CT scan of the chest CT scan of the abdomen and pelvis Bone scan for evaluation of distant metastasis Tumor markers (CEA and CA15.3 or CA27.29) may also be obtained in these patients

Breast Cancer Treatment
Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Lumpectomy Mastectomy Breast Reconstruction Management of Contralateral breast Sentinel Node Dissection Axillary Lymph node dissection Breast Conserving radiation therapy Adjuvant Chemotherapy Adjuvant Hormonal Therapy Behavioral therapy--- Very Important

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Lumpectomy Defined as complete surgical resection of a primary tumor Goal of achieving widely negative margins (ideally a 1 cm margin around the lesion) Synonyms for lumpectomy Partial mastectomy Segmental mastectomy Tylectomy A quadrantectomy is a type of lumpectomy Complete removal of the entire affected breast quadrant Performed with palpation guidance or with image guidance NSABP-B6 did find a significant difference in the rate of local recurrence between the 3 treatment arms. Patients in the lumpectomy alone without radiation therapy group had a significantly higher local recurrence rate than patients undergoing lumpectomy plus radiation therapy (39.2% vs 14.3%, respectively). Patients who underwent modified radical mastectomy had a 10.2% risk of chest wall recurrence. This landmark study established breast-conserving surgery with radiation therapy to be equivalent to modified radical mastectomy.

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Mastectomy Total mastectomy Complete removal of all breast tissue Clavicle superiorly Sternum medially Inframammary crease inferiorly Anterior axillary line laterally with en bloc resection of the fascia of the pectoralis major The nipple-areolar complex (NAC) is resected along with a skin paddle to achieve a flat chest wall closure when performing a total mastectomy. No removal of any axillary nodes Modified radical mastectomy Total mastectomy with axillary lymph node dissection

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Postmastectomy Radiation Therapy Positive postmastectomy margins Primary tumors larger than 5 cm Involvement of 4 or more lymph nodes Breast Reconstruction SSM NSM

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Management of Contralateral breast Sentinel Node Dissection Technetium 99 Methylene blue dye First set of nodes that drain from the breast to the axilla Lymph nodes checked for metastasis If positive usually recommend axillary dissection Axillary Lymph node dissection

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Breast Conserving radiation therapy Used to eliminate residual subclinical disease Side effects Fatigue Breast pain Swelling Skin desquamation Late toxicity (lasting 6 mo or longer following treatment) Persistent breast edema Pain Fibrosis Skin hyperpigmentation

Epidemiology Etiology Risk Factors Screening Presentation Workup Staging Treatment Adjuvant Chemotherapy Adjuvant Hormonal Therapy Estrogen-receptor positive early stage breast cancer Hormonal therapy plays a main role May be used with chemotherapy Function to decrease estrogen's ability to stimulate existing micro-metastases or dormant cancer cells Can reduce the relative risk of distant, ipsilateral, and contralateral breast cancer recurrence by up to 50%

Breast Cancer Any questions?
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Breast Cancer A Family Medicine Perspective

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