Breast Conference 9/7/2011

LP 60 AAF presenting with a left breast mass The patient noticed a lump in her left breast 10 years ago. She then had a mammography and ultrasound which were interpreted as benign, according to the patient. Three years ago the lesion began to grow gradually. The patient did not have any evaluation of the lesion, and just recently saw her primary care, who referred her for further evaluation of the lesion.

LP Menarche: 13y G3P2 (15y), breastfeeding: none OCP: 21y HRT: none Postmenopausal (55y) Hx breast bx: none Hx breast Ca: none Fhx: father – multiple myeloma (60y), sister – renal cell carcinoma Shx: caffeine (rarely), soy(-), tobacco (past smoker), ETOH (rarely) Smoked 1 pack/day for 30 years, quit 14 years ago She had trauma to the left breast many years ago that resolved in swelling that gradually resolved spontaneously

LP PMH: s/p MI PSH: Unilateral oophorectomy d/t ectopic pregnancy Meds: Singulair, Albuterol, Lisinopril NKDA Uses singulair and albuterol rarely

LP PE: Right breast: Left breast: Left axillary adenopathy Within normal limits Left breast: Nipple areolar complex replaced by tumor Central 4 cm mass Left axillary adenopathy

LP Radiology: Diagnostic mammogram: US: Left breast: mass with a spiculated margin central to the nipple in the retroareolar region Left axilla: multiple enlarged nodes US: Left breast: 3.9*3.1*2.4cm irregular mass central to the nipple. Adjacent 2.1*1.3*2cm oval mass Left axilla: multiple enlarged nodes, hypoechoic with no fatty hilum 6

LP Radiology: MRI: Scheduled PET/CT: 7

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LP Pathology: Breast lesion: Axillary lesion: infilrating ductal carcinoma, grade 3 ER, PR, HER2 - pending Axillary lesion: Metastatic ductal carcinoma

LP 60 F clinical stage IIIB, T4bN1M0

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LP Surgery – Medical oncology – Radiation oncology – Plastic surgery – Mastectomy + ALND Medical oncology – Neoadjuvant chemotherapy Radiation oncology – Plastic surgery – Genetics – Psychosocial –

GM 68 AAF presenting with an abnormal mammogram

GM Menarche: 11y G8P5 (19y), breastfeeding: 1 month OCP: none HRT: none Postmenopausal Hx breast Ca: none Fhx: none Shx: caffeine(+), soy(-), tobacco(-), ETOH(-) Bra: 44C

GM PMH: HTN, DM, GERD, uterine fibroids PSH: none Meds: Nexium, Cozaar, NovoLog, Lantus NKDA On review of systems she has no other complaints

GM PE: Right breast: Left breast: Within normal limits Palpable mass, 9 o’clock 8cm from nipple Left breast: Within normal limits No axillary, supraclavicular or cervical lymphadenopathy

GM Radiology: Screening mammogram: US: Right breast: Cluster of masses at 9 o’clock middle depth US: Right breast: irregular hypoechoic mass, 9 o’clock, 13cm from nipple, 1.1*1.4*1cm, with an adjacent 0.5*0.6 cm posterior mass No axillary adenopathy 19

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GM Pathology: Right breast lesion: Infiltrating ductal carcinoma, grade 2 ER(+) PR(+), HER2(-)

GM 68 F, clinical stage IA/IIA T1c/2N0M0

GM Surgery – Medical oncology – Radiation oncology – Plastic surgery – Partial mastectomy vs. mastectomy + SLNB Medical oncology – Radiation oncology – Plastic surgery – Genetics – Psychosocial –

DH 77 AAF presenting with an abnormal mammogram

DH Menarche: 14y G8P8 (17y) Postmenopausal (early 40’s) Hx breast bx: none Hx breast Ca: none Fhx: son – colon cancer (33y) Shx: tobacco (+), ETOH(-) Bra: C

DH PMH: HTN, PVD, HLD, DM PSH: Meds: Allergies: Talwin, Aspirin s/p Whipple procedure 5/2011 – serous cystadenoma Complicated by anastomotic leak s/p colon resection d/t cancer – 1982 AAA Thyroid nodules s/p hysterectomy Meds: Amlodipine, Clonidine, Creon, Colace, Lisinopril, Omeprazole, Pravastatin Allergies: Talwin, Aspirin On review of systems she has no other complaints

DH PE: Right breast: Left breast: Nodularity over right thyroid lobe Right breast: Palpable mobile mass 5-6 o’clock, nipple inversion Left breast: Within normal limits No axillary, supraclavicular or cervical lymphadenopathy

DH Radiology: CT: Diagnostic mammogram: US: Right breast: 1.5cm nodule, medial aspect Diagnostic mammogram: Benign bilateral calcifications Right breast: round mass with a spiculated margin 5 o’clock Density – 10 o’clock US: 1.7*1.9*1.2cm lesion, 5 o’clock, 4cm from nipple, two 6 and 9mm satellite nodules Cluster of lymph nodes 10 o’clock Thyroid: multinodular goiter 31

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DH Pathology: Breast lesion 5 o’clock: Invasive mucinous carcinoma ER(+) PR(-), HER2(+1) Grade 2

DH 77 F, clinical stage IA, T1cN0M0 mucinous carcinoma

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DH Surgery – Medical oncology – Radiation oncology – Plastic surgery – Biopsy of 10 o’clock lesion Partial mastectomy vs. mastectomy + SLNB Medical oncology – Radiation oncology – Plastic surgery – Genetics – Psychosocial –

SS 52 AAF presenting with a mass on left mastectomy scar 1994 – T2N0M0 Left breast lobular carcinoma ER/PR+, HER2 unknown Modified radical mastectomy, reconstruction Chemotherapy

SS Menarche: 12y G3P3 (14y), breastfeeding: none OCP: none HRT: none Postmenopausal (51y) Fhx: none Shx: caffeine(+), tobacco(+) Bra: 44D

SS PMH: DM, HTN, HLD, CRF, arthritis PSH: Meds: Allergies - Compazine MRM + reconstruction (saline implant) - 1994 right breast reduction – 1997 Colectomy – 1997 Meds: Metformin, Avandia, Prilosec, Ditropan, Naproxen, Percocet, Lisinopril Allergies - Compazine On review of systems she has no other complaints

SS PE: Right breast: Left breast: s/p reduction mammoplasty Left breast: s/p mastectomy, reconstruction s/p excisional biopsy No axillary, supraclavicular or cervical lymphadenopathy

SS Radiology: Diagnostic mammogram: US: MRI: 4/2011 – no significant abnormalities US: 4/2011 - no significant abnormalities MRI: Limited exam PET/CT: no evidence of metastasis 44

SS Pathology: Breast lesion (excisional biopsy): Infiltrating lobular carcinoma 2.8cm Involving dermis and subcutaneous tissues Positive margins ER(+) PR(+), HER2(+2, -FISH)

SS 52 F, recurrent lobular carcinoma, left breast

SS Surgery – Medical oncology – Radiation oncology – Plastic surgery – Resection Medical oncology – Radiation oncology – Plastic surgery – Implant removal Genetics – Psychosocial –

Concepts in ALND Contribution of local therapy to breast cancer survival is controversial Biological factors may effect selective invasion to lymph nodes rather than visceral organs Lymph node tumor status influences but not dictates chemotherapy Earlier detection reduces incidence and number of nodal metastases Just as certain tumor types metastasize to certain organs and not others.

Is axillary lymph node dissection really necessary? Aim: determine the effects of ALND on overall survival in patients with SLN metastases treated with lumpectomy, adjuvant systemic therapy and radiation Multicenter randomized phase 3 trial

Inclusion: Adult women Histologically confirmed invasive breast carcinoma Clinically 5cm or less No palpable adenopathy SLN containing metastatic breast cancer (FS, touch or H&E) Lumpectomy to negative margins IHC identified only - ineligible

Exclusion: 3 or more positive SLN’s Matted nodes Gross extranodal disease Neoadjuvant therapy (hormonal or chemotherapy)

Disease characteristics were balanced between the groups Stratification: Age (50y) ER status Tumor size (≤1cm, >1 and ≤2cm, >2cm) Disease characteristics were balanced between the groups Whole breast radiation Adjuvant systemic therapy determined by physician

Endpoints: Primary: Secondary: Overall survival (time from randomization until death from any cause) Occurrence of sugical morbidities Secondary: Disease free survival (time from randomization to death or first documented recurrence of breast cancer) Recurrence: locoregional or distant Non

Non inferiority study: OS not less than 75% of that reported for ALND (80% at 5y, based on literature) HR for mortality less than 1.3 compared to ALND Base model: SLND vs. ALND Age Adjuvant treatment Prognostic variables added individually

Median follow up - 6.3 years Extremely low mortality rate (94 deaths) Decision to terminate the study Even if all 1900 were accrued, it would take more than 20 years of follow up to reach 500 deaths None of the planned interim analyses were performed

No significant difference in OS between the groups (92.5% vs. 91.8%) No significant difference in DFS between the groups (83.9% vs. 82.2%)

HR (comparing OS between two groups) – Unadjusted: 0.79 Adjusted for adjuvant therapy and age: 0.87 HR (comparing DFS between two groups) – Unadjusted: 0.82 Adjusted for adjuvant therapy and age: 0.88

Locoregional recurrence – similar between groups Axillary nodal recurrence rate 0.9% in SLNB only group (total locoregional recurrence – 2.5%) High rate of locoregional control with multimodality therapy, even without ALND Higher rate of surgical morbidities in ALND group

No benefit from addition of ALND in terms of: Local control Disease free survival Overall survival Knowing the number of positive nodes is unlikely to change systemic therapy decisions ALND still standard practice: Mastectomy Lumpectomy without radiotherapy Partial breast irradiation Neoadjuvant therapy Prone position radiation