Malignant Breast Disease Juhi Asad, DO Alison Estrabrook, MD Dept. of Breast Surgery

Breast Cancer Over 180,000 new cases ~62,000 are in situ (30%) 2nd leading cause of all cancer deaths 80% of cases occur >50yo In situ cases have stablized since late 1990s due to early detection~40,000 deaths will occur due to breast cancer in 2007

Pre-op History Physical Imaging Diagnosis Treatment options

Surgical Options Partial Mastectomy (lumpectomy) Total Mastectomy Reconstruction Sentinel lymph node biopsy Axillary lymph node dissection

Surgical Treatment Partial Mastectomy Radiation therapy Free margins Aesthetic results NSABP B-06 no significant difference in survival between MRM, lump w/radiaton, and lump w/o radiation

Partial Mastectomy Contraindications Size relative to breast Multifocality Early pregnancy Inability to receive radiation Connective tissue disease Prior radiation

Surgical Treatment Radial Mastectomy Historical – mid 70s Breast, pectoralis, regional lymph nodes along axillary vein to costoclavicular ligament

Surgical Treatment Total Mastectomy axillary dissection TM + Skin sparing w/reconstruction

Reconstruction Implants Flaps TRAM Latissimus DIEP

Tissue Expanders

TRAM

Oncoplastic Surgery

Preop 4 Days Postop

Surgical Treatment Sentinel Node Biopsy The 1st node in the ipsilateral axilla to drain the tumor >97% concordance rate

Sentinel Lymph Node Contraindications Clinically positive lymph nodes

Sentinel Lymph Node Technetium-99m sulfur colloid Isosulfan blue dye Intradermal : peritumoral or periareolar Isosulfan blue dye Intraparenchymal Problems: Anaphylactic reaction (1-3%) Skin discoloration Contraindicated in pregnancy

Sentinel Lymph Node Intra-op evaluation Frozen section Touch prep Benefits over axillary node dissection more accurate pathology less lymphedema – ( very rare vs 10-50%) less sensory disturbances less shoulder dysfunction less wound infection less incisional pain

Axillary Lymph Node Dissection Indications Clinically + nodes + SLN Level I & II

Pathology DCIS Invasive Ductal Invasive Lobular

DCIS 200% b/w 1983-1992 15-30% all screen-detected tumors Diagnosis Screening mammogram Microcalcifications Linear, heterogenous Biopsy Stereotactic Open biopsy

DCIS Treatment Partial Mastectomy Total mastectomy Followed by radiation +/- hormonal therapy Total mastectomy Diffuse disease Multifocal Persistent positive margins Inability to give radiation Patient choice

DCIS Sentinel Lymph Node Biopsy Total Mastectomy Palpable mass Microinvasion

DCIS Radiation Therapy Hormonal Therapy 50% decrease in recurrence LE NSABP B-24 – LE, RT, +TAM vs LE, RT only TAM – 8.2% incidence of IBTR Placebo – 13.4% incidence of IBTR

Invasive Ductal Ca Most common – 50-70% of invasive ca

Invasive Lobular Ca 10-15% of breast ca Fail to form masses Multifocal and multicentric Bilateral – 20-29%

ILC

Staging Primary Tumor (T) TX: unable to assess T0: no evidence of primary tumor Tis: DCIS, LCIS or Paget’s (nipple only) T1: <2cm T2: 2cm-5cm T3: >5cm T4: extension

Regional Lymph Nodes (N) NX: unable to assess N0: negative N1: 1-3 nodes N2: 4-9 nodes N3: >10 nodes

Distant metastatsis: (M) MX: unable to assess M0: negative M1: distant mets

AJCC Staging Stage 0 Stage I Stage IIA Stage IIB Stage IIIA Stage IIIB Tis, N0, M0 Stage I T1*, N0, M0 Stage IIA T0, N1, M0 T1*, N1, M0 T2, N0, M0 Stage IIB T2, N1, M0 T3, N0, M0 Stage IIIA T0, N2, M0 T1*, N2, M0 T2, N2, M0 T3, N1, M0 T3, N2, M0 Stage IIIB T4, N0, M0 T4, N1, M0 T4, N2, M0 Stage IIIC** Any T, N3, M0 Stage IV Any T, Any N, M1 [Note: T1 includes T1mic]

5 year Survival Stage 5-year Relative Survival Rate 100% I IIA 92% IIB 100% I IIA 92% IIB 81% IIIA 67% IIIB 54% IV 20%

Adjuvant Therapy www.adjuvantonline.com Assess the risks and benefits of additional therapy after surgery

Prognostic Indicators Hormone Receptors – improved prognosis ER – 70-80% PR – indicator for a functional ER receptor Epidermal growth factor HER/erbB2 EGFR HER2/neu Cell proliferation & differentiation erbB2

Prognostic Indicators P53 – tumor suppressor gene Overexpression of p53 Poorer prognosis Shorter disease-free and survival

Oncotype Dx ER (+); node (-) Genetic profile – 21 gene assay Recurrence score (3 groups) Low – hormonal therapy Intermediate – TailorRx trial Hormonal vs chemo + hormonal High – chemo + hormonal therapy

Adjuvant Therapy Hormonal therapy Antiestrogen therapy – Tamoxifen Pre & post-menopausal women Reduces risk of contralateral disease & mets Side effects Endometrial ca Thromoembolic events

Adjuvant Therapy Hormonal Therapy Aromastase Inhibitors – blocks the conversion of androstenedione to estrone Post-menopausal women ATAC trial – anastrozole decreased the risk of contralateral cancers compared to TAM Side effects Bone loss and joint pain

Adjuvant Therapy Chemotherapy Size of tumor Nodal status ER/PR HER2/Neu -- Herceptin

Node (-) & ER/PR (+) & T<1cm & HER2 (-) & no LVI Low Risk Node (-) & ER/PR (+) & T<1cm & HER2 (-) & no LVI -- Hormonal therapy -- consider Oncotype Intermediate Risk Node (-) & at least 1 of the following T>2cm grade II/III LVI <35 yo HER2 (+) Node + (1-3) & HER2 (-) ER/PR (+) -- OncotypeDX -- hormonal therapy -- Chemo & hormonal therapy ER/PR (-) -- Chemo High Risk Node + (1-3) & HER2 + Node +(>4) -- Chemo & hormone

LCIS Incidental finding Marker for an increased risk 0.8-8% of breast biopsies Marker for an increased risk 1% per year risk Bilateral breasts Most common – Ductal carcinoma

LCIS Treatment Annual mammograms 6mos CBE Discuss bilateral prophylactic mastectomies

Paget’s Disease Chronic, eczema-like rash of the nipple and areolar skin ~97% underlying Ca Diagnosis Punch biopsy Core needle biopsy

Paget’s Disease Treatment Surgical treatment Adjuvant therapy TM w/ SLN Central segmentectomy w/ SLN  XRT Adjuvant therapy Chemotherapy Hormonal therapy

Locally Advanced Disease Large tumors (>5cm) Chest wall involvment Ulcerations Fixed axillary lymph nodes

Locally Advanced Disease

Locally Advanced Disease Treatment Neoadjuvant therapy – 80% shrinkage Downstage BCT vs Mastectomy radiation

Post Neoadjuvant therapy

Inflammatory Breast Ca Rare & aggressive Accounts for 5% of all breast ca Younger women higher tendency for distant mets AJCC – T4d Stage IIIB Stage IIIC Stage IV

Inflammatory Breast Ca Presentation Rapid onset of erythema, edema (peau d’orange Often no mass Axillary node involvement Imaging No distinct mass Skin thickening Trabecular thickening

Inflammatory Breast Ca Histology Dermal lymphatic invasion Not associated with a subtype High S-phase fraction Mutation of p53

Inflammatory Breast Ca Survival 3yr – 40-70% 5 yr – 50% 10 yr – 26.7%

Male Breast Cancer 1% of all breast ca >90% Ductal Ca ER/PR + 5-10% are hereditary BRCA 2 gene

Breast CA during Pregnancy 1 in 3,000 pregnancies Most common non-GYN cancer Present as a painless mass Worse prognosis Advanced stage Stage II-III 75% rate (median 40mos) Hyperestrogenic state

Breast Ca during Pregnancy Diagnosis Ultrasound Mammogram Core needle biopsy

Breast Ca during Pregnancy Treatment 1st trimester TM with SLN bx Chemotherapy Significant risk of spontaneous abortion Fetal malformation 2nd & 3rd trimester TM w/ SLN bx or Lumpectomy with SLN bx radiation

Question Following an excisional biopsy for microcalifications, the pathology report states there is LCIS present. You discuss with the patient She needs a lumpectomy then RT She would benefit from a mirror biopsy She has a future cancer risk of 1% per yr No known therapy to help her

Question 55 yo female underwent a Rt lumpectomy with SLN bx. Pathology showed a 3.5 cm well-differentiated infiltrating Ductal ca. The sentinel lymph nodes were negative (0/2). No evidence of any distance mets. What is her stage?

40 yo woman presents with a 2cm mass in her right breast first detected by mammo. A core biopsy reveals infiltrating ductal ca. She has no palpable lymph nodes. Appropriate therapy for the patient would include: -- partial mastectomy -- sentinel lymph node biopsy -- consideration of adjuvant chemo -- radiation therapy -- all of the above