PCCSOM 2026 Medicine 2 M.10 Breast Cancer PDF

PCC SOM 2026 MEDICINE 2 M.10 BREAST CANCER Early menarche (12 y/o) MEDICINE LECTURE...

PCC SOM 2026 MEDICINE 2 M.10 BREAST CANCER Early menarche (12 y/o) MEDICINE LECTURE Late first full-time pregnancy (35 y/o) LECTURER: Dr. Jezreline Marie Cacanindin-Rimando Exogenous hormone replacement therapy DATE: October 16, 2024 Women without functioning ovaries, or who experience an early menopause, and who never receive combination TOPIC OUTLINE estrogen/progesterone replacement therapy, are much less INTRODUCTION likely to develop breast cancer than those who have a EPIDEMIOLOGY normal menstrual history. RISK FACTORS Genetic Considerations - Hormone replacement therapy (HRT) with PREVENTION of BREAST CANCER conjugated equine estrogens plus progestins SCREENING FOR BREAST CANCER 6–7 years of HRT nearly doubled the risk of EVALUATION OF BREAST MASSES in MEN and WOMEN breast cancer and increases the risk of The palpable Breast Mass cardiovascular events The Abnormal Mammogram Decreases the risk of bone fractures and Breast masses in the pregnant or lactating colorectal cancer woman - Sex, Age, and Hormonal exposure Benign breast masses - Role of diet in breast cancer etiology is controversial STAGING Associative links exist between breast cancer risk Noninvasive breast cancer and total caloric and fat intake, but the exact role Invasive breast cancer of fat in the diet is unproven TREATMENT - Central Obesity, Metabolic Syndrome, DM Type 2, THERAPY OF METASTATIC DISEASE Depression MALE BREAST CANCER ☺ Associated with both occurrence and recurrence of breast cancer INTRODUCTION - Atypical hyperplasia and radial scars - Breast cancer is a MALIGNANT proliferation of - Prior radiation (in adolescence or early child-bearing epithelial cells lining the ducts or lobules of the ages). For example, Hodgkin Lymphoma breast. Women who have been exposed to radiation - Epithelial malignancies of the breast are the most before the age 30 years common cause of cancer in women (excluding skin Radioactive iodine therapy for thyroid disease is cancer)- 1/3 of all cancers in women NOT associated with increased risk of breast - Mortality rate from breast cancer has begun to cancer decrease by more than 1/3 over the past three - Family History decades in high and middle-income countries A woman with a FIRST-DEGREE RELATIVE (mother or a sister) with breast cancer has an EPIDEMIOLOGY and RISK FACTORS increased relative risk of approximately 30-50% (or one-third to one half higher) - GLOBAL CANCER OBSERVATORY 2022 - WORLD Only occurs for 1-15% all breast cancers Most women do not have a strong family history SECOND most common cancer - BRCA 1 and BRCA 2 FOURTH most common cause of cancer death - PHILIPPINES Breast cancer susceptibility genes SECOND most common Women who inherit a mutated allele of this gene from either parent have at least a SECOND leading cause of death second to LUNG 60–80% lifetime chance of developing breast CANCER cancer RISK FACTORS 33% chance of developing ovarian cancer Cancers that arise within a BRCA1-mutated - Seventy-five percent of all breast cancers occur in patient are almost exclusively negative for women aged >50 years estrogen and progesterone receptors (ER, PgR) - Sex hormone-dependent disease through increased and for human epidermal receptor 2 (HER2) activity of the estrogen receptor (ER) and its ligands, (“triple negative” breast cancers) estradiol and estrone Approximately 20% of women with triple - Relative exposure to both endogenous and negative breast cancers will be positive for exogenous estrogens increases the risk of breast deleterious germline BRCA1 SNPs cancer NOTE TAKER:BALAO-AS | BASTIAN | CUTAY | DOMINGO | FERRER | GARCIA | PADAYAO Page 1 | 6  PCC SOM 2026 MEDICINE 2 M.10 BREAST CANCER Risk of breast cancer penetrance is variable EVALUATION OF BREAST MASSES in MEN and within the BRCA1-affected population WOMEN Higher among women born after 1940, presumably due to promotional effects of PALPABLE BREAST MASSES hormonal factors. Men who carry a mutant allele of the gene have - Most newly diagnosed breast cancers are an increased incidence of prostate cancer and asymptomatic breast cancer. - Features that are worrisome for breast cancer: - TESTING for BRCA 1 and BRCA 2 mutations Firmness, irregularity, tethering or fixation to the Triple-negative breast cancer underlying chest wall, and dermal erythema or 95% follow-up, further evaluation and biopsy (if - CHEMOPREVENTION appropriate) are indicated Selective estrogen receptor modulators (SERMs) o Tamoxifen and Raloxifene are e􀁷ective BREAST MASSES IN THE PREGNANT OR LACTATING methods to lower breast cancer risk WOMAN Aromatase inhibition in postmenopausal women - Breast cancer develops in 1 in every 3000–4000 o Lowers risk of ER-positive breast cancer pregnancies by approximately one-third to one-half, - Pregnant women often have more advanced disease o Although it has no effect on the more than premenopausal women lethal ER-negative breast cancers. - Persistent lumps in the breast of pregnant or - PROPHYLACTIC BILATERAL OOPHORECTOMY and lactating women cannot be attributed to benign SALPINGO-OOPHORECTOMY changes based on physical findings; such patients Performed in women with high genetic risk (such should be promptly referred for diagnostic as those with inherited BRCA1/2 deleterious evaluation. SNPs) Reduces the risk of ovarian or breast cancer BENIGN BREAST MASSES - Only approximately 1 in every 5–10 breast biopsies SCREENING FOR BREAST CANCER leads to a diagnosis of cancer - SCREENING MAMMOGRAPHY - Majority of benign breast masses are due to Earlier diagnosis and subsequent local and “fibrocystic” changes, a descriptive term for small systematic therapy fluid-filled cysts and modest epithelial cell and fibrous Reduces breast cancer mortality by one-quarter tissue hyperplasia. to one-third in women aged ≥50 years. - Subset of women with ductal or lobular cell - Self-examination or physical breast examination by a proliferation is approximately 30% of patients health professional Particularly the small fraction (3%) with atypical Screening for ages 45 hyperplasia Poor sensitivity and specificity Fourfold greater risk of developing breast cancer Not recommended than those women who have not had a biopsy NOTE TAKER:BALAO-AS | BASTIAN | CUTAY | DOMINGO | FERRER | GARCIA | PADAYAO Page 2 | 6  PCC SOM 2026- MEDICINE 2 M.10 BREAST CANCER Patients with a benign biopsy without atypical INVASIVE BREAST CANCERS hyperplasia are at little risk and may be followed - 85% - ductal in origin routinely. - 10% - lobular or mixed ductal/lobular - 5% - 'special types* - mucinous or colloid, tubular, STAGING medullary or papillary - STAGING NONINVASIVE BREAST CANCERS Tumor size (T) - DUCTAL CARCINOMA IN SITU (DCIS) Presence of absence of regional nodes (N) Proliferation of cytologically malignant breast Distant metastasis (M) epithelial cells within the ducts Staging can be performed clinically (cTNM) or “Premalignant condition” pathologically (pTNM) o At least one-third of patients with Before or after (yTNM) adjuvant systemic untreated DCIS develop breast cancer therapy within 5 years o Manny low grade DCIS do not appear to TREATMENT progress over many years; many patients are overtreated EARLY-STAGE BREAST CANCER NO reliable methods to distinguish patients who - GOAL of therapy: CURE; substantial survival require treatment from those who may be safely prolongation observed - Primary therapy - surgery, radiation therapy Mastectomy is 100% effective in preventing Directed towards the breast and loco regional future breast cancer lymph nodes Breast Preserving Therapy: excision surgery Minimize the odds of locoregional recurrence, alone with or without breast radiation while maintaining quality of life and cosmesis - High risk for local recurrence: - Systemic therapy - adjuvant treatment Extensive disease within the breast Chemotherapy, endocrine therapy, anti-HER2 Age < 40 Treats micrometastases that may have already Cytologic features escaped to distant sites but are not yet o Necrosis detectable o Poor nuclear grade - Prognostic factors o Comedo Subtype How likely a cancer will recur either locally or in o Over-expression of HER2 distant organs in the future il a patient is not - LOBULAR CARCINOMA IN SITU (LCIS) treated with the respective treatments Presence of malignant cells within the lobules - Predictive factors Does not usually cause palpable breast masses, Used to determine if a given treatment is likely nor does it often induce suspicious findings on to work or not mammogram - Anatomic prognostic factors Usually found as an incidental finding during Locally advanced breast cancer (T4 lesions: skin pathologic examination of a breast biopsy done erythema “inflammation”, or edema “peau d for some other reason orange”, nodules, or ulceration or tumor fixation Often spread throughout the breast to the chest wall) Frequently found on the contralateral breast Tumor size (T) and lymph node status (N) - most sent important prognostic factors Increased risk of a subsequent breast cancer - Biologic features Bilateral prophylactic mastectomy Histologic tumor grade New, invasive cancer in either breast at a rate of ER, PR and HER2 status approximately 1% per year over at least the next 15-20 years, and probably lifelong if untreated SUBTYPES OF BREAST CANCER More commonly considered a pre-malignant condition than DCIS 1. LUMINAL A Management options: careful observation with - Generally, ER (Estrogen Receptor) positive, almost routine mammography and chemoprevention universally low or negative in HER, low-grade, have with Tamoxifen or Aromatase Inhibitor low proliferative thrust With capacity to metastasize and cause - Have a generally FAVORABLE prognosis substantial morbidity and mortality - Responsive to hormonal therapy - May be less responsive to chemotherapy NOTE TAKER:BALAO-AS | BASTIAN | CUTAY | DOMINGO | FERRER | GARCIA | PADAYAO Page 3 | 6  PCC SOM 2026 LUMINAL B MEDICINE 2 M.10 BREAST CANCER ADJUVANT REGIMENS - PR negative, may express HER2 but of low levels, usually higher grade and have higher proliferative ENDOCRINE THERAPY activity than luminal A tumors - Indicated for all patients with ER-positive breast - Prognosis is worse than Luminal A cancers cancer - May be more responsive to chemotherapy - Selective Estrogen Receptor Modulators (SERM): Tamoxifen 2. HER-2 AMPLIFIED Prevents new cancers and reduces the risk of - Exhibit co-amplification and over-expression of other locoregional recurrences (DCIS) genes adjacent to HER2. Reduces risk of distant recurrence and death due - Prognosis was poor historically, but has now to invasive breast cancer improved with introduction of targeted anti-HER2 Equally effective in pre- and post-menopausal therapies women, but slightly less effective in very young - The advent of trastuzumab and other targeted patients therapies, the clinical outcome of HER2 positive - Aromatase Inhibitors (Al): Letrozole, Anazole, patients is markedly improved compared to 20 or Exemestane more years ago. CHEMOTHERAPY 3. BASAL - Multiple-agent adjuvant chemotherapy is more - Negative for ER, PR and Her2 effective than single-agent chemotherapy - “Triple negative” - Alkylating agent (Cyclophosphamide), anthracyclines - Characterized by markers of basal/myoepithelial (Doxorubicin, Epirubicin), anti-metabolites (5 cells. Fluorouracil, Capecitabine, Methotrexate), taxanes - Usually high-grade tumors (Docetaxel, Paclitaxel) and the platinum salts - Germline BRCA 1 mutations (Cisplatin, Carboplatin) - Which regimen is appropriate for a patient must be 4. NORMAL BREAST-LIKE individualized based on prognosis, comorbid - Gene Expression: reminiscent of nonmalignant conditions, and the perspective of the patient “normal” breast epithelium - Prognosis is similar to the luminal B group NEOADJUVANT CHEMOTHERAPY - “Pre-operative” 5. CLAUDIN-LOW - Administration of adjuvant systemic therapy before - Often “triple negative” definitive surgery and radiation therapy - Low expression of cell-cell junction proteins including - Many patients will be “downstaged” E-cadherin. - Patients who achieve a pathologic complete response - They are frequently associated with lymphocytic (PGR) have a substantially improved survival infiltration. compared to those who do not - It is essential that all patients, regardless of response LOCAL (PRIMARY) TREATMENTS to neoadjuvant chemotherapy, receive adjuvant - Modified radical mastectomy endocrine therapy if they have an ER-positive breast Chest wall muscles are preserved: Only a cancer and adjuvant anti-HER2 therapy if their cancer sampling of axillary lymph nodes are removed is HER2 positive. - Breast-conserving treatments TOXICITIES of CHEMOTHERAPY Surgical excision of the primary tumor - Nausea, vomiting and alopecia: nearly 100% of (lumpectomy, quadrantectomy, or partial patients mastectomy) often followed by loco regional - Potential life-threatening or life-changing toxicities In radiation 2-3% of all treated patients Contraindications: Neutropenia, fever o Large tumor to breast ratio Secondary myelodysplasia and leukemia o Inability to achieve clear margins with - Anthracyclines: cumulative dose-related congestive adequate cosmesis after extensive surgery heart failure o Multifocal cancers - Taxanes: major dose-limiting and life-changing o Extensive four-quadrant DCIS toxicity of peripheral neuropathy o Inability to receive radiation - Cognitive dysfunction: “chemo-brain” NOTE TAKER:BALAO-AS | BASTIAN | CUTAY | DOMINGO | FERRER | GARCIA | PADAYAO Page 4 | 6  PCC SOM 2026 ANTI-HER 2 THERAPY MEDICINE 2 M.10 BREAST CANCER - Trastuzumab: humanized anti-HER2 monoclonal antibody Decreases both the risk of recurrence and mortality in early-stage breast cancer Given for 12 months - Cardiac dysfunction: main toxicity especially when the agent is delivered simultaneously with doxorubicin - Pertuzumab + Trastuzumab: significantly reduces distant metastasis and mortality (in patients with poor prognostic features such as positive axillary lymph nodes) METASTATIC DISEASE CHECKPOINT - 15-20% of patients treated for localized breast cancer 1. 52-year-old woman, comes to the clinic for her annual develop metastatic disease in the subsequent decade check-up. She has a family history of breast cancer—her after diagnosis mother was diagnosed at age 55. Maria started - Soft tissue, bones, lungs and liver menstruating at age 12 and had her first child at age 35. - Biopsy of suspicious lesions to confirm recurrence Which of the following is a significant risk factor for Maria’s - Many benign conditions can mimic a recurrent breast breast cancer risk? cancer A) Family history of breast cancer - Although treatable, metastatic disease is rarely if ever B) Early menarche cured C) Late first pregnancy - Median survival 95% C.) 60–80% lifetime chance of developing breast cancer D.) 33% chance of developing ovarian cancer 9.Features that are worrisome for breast cancer, especially during physical examination (palpable masses) A.) Firmness, irregularity, tethering or fixation to the underlying chest wall, and dermal erythema or peau d’ orange B.) Clustered, heterogenous, linear, and branching microcalcifications; densities C.) AOTA D.) NOTA 10. All of the following are true of the cytologic features of Ductal Carcinoma in Situ. Which one is not true? A.) Necrosis B.) Poor nuclear grade C.) Comedo Subtype D.) Over-expression of HER2 E.) NOTA NOTE TAKER:BALAO-AS | BASTIAN | CUTAY | DOMINGO | FERRER | GARCIA | PADAYAO Page 6 | 6