Breast Cancer PDF

Breast Cancer Dr. Van Den Berg Associate Professor Objectives Review the incidence and risk factors associated with breast cancer Evaluate the staging, pathology and prognostic indicators for breast cancer Compare and contrast the intrinsic breast cancer subtypes with regard to prognosis, distinguis...

Breast Cancer Dr. Van Den Berg Associate Professor Objectives Review the incidence and risk factors associated with breast cancer Evaluate the staging, pathology and prognostic indicators for breast cancer Compare and contrast the intrinsic breast cancer subtypes with regard to prognosis, distinguishing molecular markers, disease progression, and patient population Breast Cancer Most frequently diagnosed solid tumor in women – Over 290,790 new cases estimated in 2023 – 2nd most common cause of cancer death » 43,170 deaths estimated for 2023 » Deaths due to breast cancer continue to decline » 1 in 8 lifetime risk of developing » 1 in 37 risk of death Majority of women present with early stage breast cancer Age and Race as Breast Cancer Risk Screening American Cancer Society U.S. Preventative Task Force National Cancer Institute BSE Age ≥20 – risk/ benefit discussion All ages ± Periodic exam recommended CBE Age 20-39 – every 3 years All ages ± Age 20-39 – every 1-3 years Age ≥ 40 – every year Age ≥ 40 – every year ***Mammography as noted in earlier lecture. BSE – breast self-exam; CBE – clinical breast exam; ± - insufficient data to recommend for or against. Screening MRI Screening in conjunction with mammograms – High risk patients: » BRCA1 or BRCA2 gene mutation » 1st degree relative (parent, sibling, child) with a BRCA1 or BRCA2 mutation » Lifetime risk of breast cancer = 45+% or greater – Based on accepted risk assessment tools » Radiation to the chest between ages 10 and 30 Breast Cancer Risk Factors Being female: (Before age of 40 ~ rare (0.5% risk)) Previous history of breast cancer Age > 60 years (more than half of all risk) – However, numerically the highest number of pts are seen in their 40-70: (40-60~3.8% risk) (60-70~3.5%risk) (> 70~12.3% risk) – Lifetime risk 1:8 Family history of breast cancer (5 - 10%) – 1st degree relative - mother (~RR 2.0) – 2nd degree relative - aunt (~RR 1.4) Fibrocystic disease (80% of women have ‘lumpy’ breasts) (scar-like connective tissue) – Proliferative (20% of women) (~RR 1.5) » Atypical hyperplasia - in situ (4%) (~RR 3.5) Breast Cancer Risk Factors Early menarche/late menopause: – Menses beginning < 12 yo vs. > 15 yo (~RR 1.5) – Menopause at age 45 - 50 yo vs. >55 yo (~RR 1.5) Late first pregnancy/no pregnancy: – 1st pregnancy at 18 yo vs. >30 yo (~RR 2.3) Exogenous hormones: – Post-menopausal progestins (HRT) – OC’s – meta-analysis ~ no sig risk (decreases ovarian ca risk) Radiation: – Mantle radiation for Hodgkin’s disease (~RR 1.5) Genetics; (tumor suppressor genes) ( 5 - 10% of women) – BRCA 1 (chromosome 17); BRCA 2 (chromosome 13) Diet:? (fat intake & weight) – Post-menopausal obesity (~RR 1.2) Alcohol: all types of alcohol can increase risk Diagnosis History & Physical exam Mammography +/- ultrasound Biopsy – Excisional biopsy » Complete removal of abnormal tissue – Core-needle biopsy – Fine-needle aspiration (FNA) Other – Labs, chest X-ray, estrogen receptor (ER) and progesterone receptor (PR) status, HER2 overexpression, ± bone scan At diagnosis: 61% pts have localized disease, 32% regional, and 5% metastatic Staging (TNM system) Tis Carcinoma in situ T1 Tumor ≤2 cm T2 Tumor >2cm but ≤5 cm T3 Tumor >5 cm T4 Tumor of any size with extension in chest wall/skin N0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph nodes N2 Metastasis to ipsilateral axillary lymph nodes fixed to one another or to other structures N3 Metastasis to ipsilateral internal mammary lymph nodes M0 No distant metastasis M1 Distant metastasis Woodward WA, et al. J Clin Onc. 2003. Lymph Node System (Breast) A Pectoralis major muscle B Axillary lymph nodes: levels I C Axillary lymph nodes: levels II D Axillary lymph nodes: levels III E Supraclavicular lymph nodes F Internal mammary lymph nodes http://www.breastcancer.org/tre_surg_whatlymph.html Breast Cancer TNM Staging Stage 0 Stage I Stage IIA Stage IIB Stage IIIA Stage IIIB Stage IV Tis T1 T0, T1 N0 N0 N1 M0 M0 M0 T2 T2 N0 N1 M0 M0 T3 T0, T1, T2 N0 N2 M0 M0 T3 Any T N1, N2 N3 M0 M0 T4 Any T Any N Any N M0 M1 5 year Survival Based on TMN staging Stage I Stage IIA Stage IIB Stage IIIA Stage IIIB Stage IV Prognostic Indicators (other than staging) Tumor Type/Grade (1-3) How abnormal cancer cells appear Proliferation Markers – Flow cytometry (S-phase fraction) – Ki-67 Primary Tumor size HER2 status (growth factor receptor) Lymphatic/Vascular Invasion Metastatic sites (soft tissue, bone) Cianfrocca M, et al. Oncologist. 2004. Ethnicity/Age ER/PR status (Hormone receptor) Axillary Nodal Status – 0 very low risk – 1-3 low risk – 4-9 moderate risk – >10 high risk Breast Cancer Good Prognosis Patient’s age: older than 50 years Axillary nodes: not involved Size of tumor: small (< 2 cm) Local extension: absent Histologic examination: well-differentiated Cytologic study: minimally atypical (grade I) ER/PR status positive Oncogene amplification: absent – HER2 + ~ 20 - 25% of women Intrinsic Molecular Subtypes of Breast Cancer- 2000 and beyond Evaluated tumors based on gene expression patterns (~500 genes needed) to identify 5 distinct groups. Technology is not widely available to clinics. Perou et al. Nature 2000: 406; 747. Intrinsic Molecular Subtypes Risk Factors Revisited: Basal-like subtype Strong link between BRCA1 mutations or impaired BRCA1 DNA repair pathway “BRCA-ness” and developing basal-like More strongly associated with pre-menopausal breast cancer More commonly associated with women of African decent Early age of menarche is a larger risk factor for basal-like than luminal breast cancer Breastfeeding is more protective than for luminal cancers Waist-to-hip ratio (central adiposity) had stronger impact on basal-like (HR 2.3) than luminal (1.5) cancers Young age at first birth and multiparity both conferred INCREASED risk for basal-like tumors but were protective for luminal breast cancer By gene expression patterns, >70% are more similar to squamous cell lung cancer than luminal breast cancer http://www.pathophys.org/wp-content/uploads/2012/12/breastcancer-copy.png Chance of Recurrence Negative Lymph Nodes – Low risk - Intermediate risk » Tumor 2 cm » ER + /HER2 - - Age < 35yo » Age > 35yo - Cytology - Grade 2 - 3 » Cytology - Grade 1 - HER2 + OR Nodes (1-3) – High risk » HER2 (+) AND Nodes (1-3) Lymph Nodes - 4+ – High risk Disease-free interval > 2 years (low risk) Note: 75% of women are ER + Risk of Disease Recurrence (Lymph Node Involvement) Lymph Node Status* # POSITIVE Node Recurrence Risk NEGATIVE 0 Low/Minimal POSITIVE 1-3 POSITIVE POSITIVE Low 4-9 ≥ 10 Note: *Key to recurrence Medium HIGH 5-Year Survival Rates (%) (Tumor Size & Lymph Node) Tumor Size Lymph Node < 2 cm 2 – 5 cm > 5 cm NEGATIVE 96 89 82 1–3 87 80 73 ≥4 66 59 46 Distant Metastasis (Stage IV) Breast Cancer Therapeutic Options Surgery Radiotherapy Hormonal therapy Chemotherapy Immunotherapy New therapies Supportive care Treatment Early Stage Breast Cancer (Stage I/II) – Surgery → Adjuvant systemic therapy » Chemotherapy, XRT, +/- hormonal therapy (ER+), trastuzumab (HER2+) Locally Advanced Breast Cancer (Stage III) – Neoadjuvant chemotherapy +/- hormonal therapy (ER+) → surgery → XRT +/- chemotherapy/hormonal therapy (ER+) Metastatic Breast Cancer (Stage IV) – Only 6+% at diagnosis, but over 30% over course of disease – Incurable (look to extend DFP and OS) – Chemotherapy +/- hormonal (ER+) therapy, trastuzumab (HER2+) XRT = radiation therapy ER+ = estrogen receptor positive What are the treatment options? Treatment of primary disease - Surgery – Modified radical mastectomy (MRM) – Lumpectomy plus local irradiation » 5 yr survival ~ 76% vs. 85% » Failure rate ~ 7.2% vs. 8.1% Adjuvant therapy – chemotherapy is standard adjuvant treatment for moderate/high-risk pts. < 50 yo. » Survival benefit (67% vs 57%) ~ 10% – For post-menopausal women - hormone therapy » Survival benefit (53% vs 50%) ~ 3% Summary Advances in breast cancer screening have led to early diagnosis and improved outcomes. Breast cancer screening and prevention have inherent risks and can lead to overtreatment. Breast cancer constitutes different diseases with discretely different biology, risk factors (still developing), prognoses, and treatment outcomes.