Recent Advances in Breast Cancer Dr. Aparna Sreevatsa Consultant Medical Oncologist Sahyadri Narayana Multispeciality Hospital, Shimoga

Case 1 L, 46 yr old lady Breathlessness CXR Pericardial effusion Pericardial fluid cytology-Adenocarcinoma B/L mammography spiculated mass in Rt Breast

Case 2 P, 36 yr old lady 2nd trimester of Pregnancy Rt Breast lump 2 wks USG Rt Breast 2*2cm lesion FNAC inconclusive Reassured USG abdomen in 3rd trimester- liver metastasis

Case 3 L, 52 yr old lady Seizures CT Brain –multiple SOL Examn- Left breast lump with left axillary lymph nodes Biopsy breast lump- invasive ductal cancer

Introduction Breast cancer is the most common malignancy in USA.

Indian Scenario(ICMR 2012-2014) Breast Cancer most common cancer (36 cases/1 lakh popln) Bangalore Thiruvananthapuram Chennai Pune Incidence of male breast cancer increasing

Pathogenesis Genetic disease Imbalance between oncogenes and tumor suppressor genes Deficient DNA repair mechanism Multistep carcinogenesis

Risk Factors Age Estrogen Early menarche Late menopause Nulliparity Age at first child >35yrs Benign breast lesions with proliferative features Smoking Alcohol Obesity

Genetics (BRCA 1 &2)

Pathology & Molecular Biology

Immunohistochemistry Estrogen and Progesterone Receptor HER2/erb B2

Molecular Types

Molecular types Hormone receptor-positive HER2-negative patients Hormone receptor-positive HER2-positive patients Hormone receptor-negative HER2-negative patients Hormone receptor-negative HER2-positive patients

Staging and Management Stage Localised (I & II) Locally advanced (III) Metastatic (IV)

Localised disease( Stage I & II) Local control Surgery Breast Conservation Prevent Recurrence Radiotherapy Chemotherapy Endocrine therapy/HER2 targetted agents

Locally advanced disease (Stage III) Downstage Chemotherapy/HER2 targetted therapy Local control Surgery Breast Conservation/MRM Prevent Recurrence Radiotherapy Chemotherapy Endocrine therapy/HER2 targetted agents

Metastatic disease (Stage IV) Systemic therapy Chemotherapy Endocrine therapy HER2 targeted agents Bisphosphonates Local therapy Palliative- Radiotherapy (bone, brain mets)

Chemotherapy q 3 wks Taxane Dosage Remarks Docetaxel 80 to 100 mg/m2 more myelosuppressive Paclitaxel 80 to 100 mg/m2 on days 1, 8, and 15 of a 28-day cycle neuropathy and myalgia are greater ; mild-moderate hepatic dysfunction Nab-paclitaxel 150 mg/m2 Q 3 wks Hypersensitivity reactions. Hyperglycemia

Anthracyclines Anthracycline Dosage Remarks Doxorubicin doxorubicin 60 mg/m2 q 3 weeks US Epirubicin Europe Pegylated liposomal doxorubicin 50 mg/m2 q 4 weeks or Lower cardiotoxicity, higher rate of plantar-plantar erythrodysesthesia

Platinum agents  Combination regimen, where DNA damage repair pathways are impaired (BRCA1 mutations and patients with triple-negative breast cancer)

Ixabepilone ixabepilone (40 mg/m2 every 21 days) ORR of 19 percent median duration of response of 5.7 months Median OS was 8.6 months. Grade 3 and 4 peripheral sensory neuropathy occurred in 14 percent of patients Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007;25(23):3407.

Eribulin 1.4 mg/m2 days 1 and 8 every 21 days less neuropathy(5%) phase III trial of 762 heavily pretreated patients who were randomly assigned to treatment with eribulin or other chemotherapy (based on physician’s and patient’s choice) (EMBRACE) significantly improved OS (median, 13.1 versus 10.6 months grade 3 and 4 neutropenia in 45 percent of patients, and grade 3 and 4 febrile neutropenia in 5 percent

Non-anthracycline, taxane-based regimens Gemcitabine plus paclitaxel or docetaxel —  Gemcitabine(1250 mg/m2 on days 1 and 8) plus paclitaxel(175 mg/m2 on day 1) ORR of 41 % gemcitabine (1000 mg/m2 on days 1 and 8) plus docetaxel(75 mg/m2 on day 1) ORR of 43 % Capecitabine plus docetaxel — Capecitabine(1250 mg/m2, twice daily for 14 of every 21 days) plus docetaxel(75 mg/m2 every 21 days) (CD) ORR of 42 %

Endocrine therapy SERM- Tamoxifen Aromatase inhibitors- Letrozole, Anastrazole, Exemestane SERD- Fulvestrant Ovarian suppression Surgical- Oophorectomy Medical- GnRH analogues(Leuprolide) Radiation Androgen receptor Enzalutamide, Abiraterone

HER2 Targeted Therapy Trastuzumab- MAB HER2 (cardiotoxic) Pertuzumab- MAB HER2 Ado Trastuzumab emtansine-MAB drug conjugate Lapatinib-TKI HER2

Trastuzumab & Pertuzumab

Breast Cancer Screening NCCN/ACS/ACOG 40yrs Every year Clinical examination+ B/L Mammography

Take Home Message Early breast cancer is a curable disease. Metastatic disease has survival ranging a few months to 2-3 years. Breast lump in pregnant & lactating mothers could be breast cancer. Screening mammography for women aged >40 years.

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