1 Welcome – 3 Apr 2017 Live Global Breast Cancer Tumor Board Locations of our attendees and panelists Boston, MA USA Quito, Ecuador Baltimore, MD USA Lviv, Ukraine Stanford, CA USA Mobile, AL USA Pennsylvania, PA USA Chicago, IL USA Boston, MA USA Boston, MA USA Durham, NC, USA Yerevan, Armenia

2 Our Standing Panelists Paul Goss MGH [email protected] Alphonse Taghian MGH [email protected] Carol Marquez Stanford University [email protected] Susan Sajer MGH [email protected] Michelle Specht MGH [email protected] Julia Tchou University of Pennsylvania [email protected] Vered Stearns Johns Hopkins [email protected] Jack Erban, Tufts Medical Center [email protected] Jennifer Plichta Duke Medical Center [email protected] Jean Wright Johns Hopkins [email protected] Ben Park Johns Hopkins [email protected] Michele Gadd MGH [email protected]

3 Our Standing Panelists Cesar Santa-Maria Northwestern Feinberg School of Medicine [email protected] Roisin Connolly, Johns Hopkins [email protected] Sharla Gayle Patterson Infirmary Health [email protected] Brittany Bychkovsky Dana Farber Harvard Cancer Center [email protected] Susan Clare Northwestern Feinberg School of Medicine [email protected] Swati Kulkarni Northwestern Feinberg School of Medicine [email protected]

4 Yerevan, Armenia Boston, USA Metaqsya Mkrtchyan, MD National Center of Oncology Insert your Photo Live Global Breast Cancer Tumor Board 3 Apr 2017

5 Case 1 – Yerevan  Q4 2016 33 y/o premenopausal woman presented to our clinic with a 1 year history of a large painful breast mass. Concomitant diseases : thyroid diffuse nodular goiter F/H of cancer: mother had cervical cancer at 45 y/o CBE: 40x32mm tumor, no skin or nipple changes, with ipsilateral mobile tender axillary lymph nodes of 17x10mm and with ipsilateral supraclavicular lymph nodes of 8x5mm. Contralateral breast exam: no palpable axillary and no supraclavicular lymph nodes.

6 Case 1 – Yerevan  Q4 2016: Mammography Right breast: no definite discrete mass lesions, suspicious microcalcifications or architectural distortions. UIQ of Left breast: high-intensity X -ray, with uneven contours about 40x32mm, two other masses of 32x25mm and 20mm were also observed next to each other. Core biopsy: Invasive Ductal Carcinoma, Grade II IHQ: ER+ve (4+3=7), PR+ve (3+3=6), HER2neu2 +, Ki67>50%, Luminal B type, FISH test of oncoprotein Her2-, Her2/ CEN-17=1.2 (negative)

7 Case 1 – Yerevan  Q4 2016: Chest/abdomen CT scan  UIQ Left breast: 40x26mm mass – enlarged 17x10mm L axillary lymph nodes  8x5mm ipsilateral supraclavicular lymph nodes.  Two 18x17mm and 14x12mm liver mets  Other organ systems are normal

8 Case 1 – Yerevan  Investigations  Complete blood count (CBC): RBC= 3.96, WBC=4.17, HB=123, PLT=322, MON=7.7, LYM=29.3  Biochemical blood analyses are within the norm  Urine analyses (UA): Specific gravity of 1011  ECG – sinus rhythm - rate 75-80bpm

9 Case 1 – Yerevan  Q4 2016 – Consensus to give neoadjuvant chemo followed by surgery to L breast – AC x 3 Adriamycin 60mg/m 2 + cyclophosphamide 600mg/m 2 3 weekly Diagnosis: Left breast cancer cT2cN3M0 Stage IIIB

10 Case 1 – Yerevan  Q1 2017: US post - 3 courses of chemo UIQ left breast: 3.0 x 2.1 cm tumor, two other masses - 0.8 x 0.6cm and 1.0 x 0.7cm observed Enlarged 1.5 cm L axillary lymph nodes Enlarged - 1.3 cm L supraclavicular lymph nodes Enlarged - 3.9 x 2.3cm L infraclavicular lymph nodes

11 Case 1 - Yerevan  Q1 2017: Considering the recent US - continue chemo with Paclitaxel After 1 course of Paclitaxel US performed: UIQ left breast: 1.9x1.5 cm tumor, two other masses of 0.6 x 0.6cm observed Left axillary lymph nodes enlarged to 1.5 cm Left supraclavicular lymph nodes enlarged to 1.3 cm Left infraclavicular lymph node group – response to 3.6x2.2cm Patient declined further chemo due to financial difficulties

12  ? Alternative treatment for this patient  ? Was it appropriate to perform surgery after only 4 courses of chemo?  ? Is hormonal therapy appropriate at this point Case 1 – Yerevan Questions and Discussion:

13 Quito, Ecuador Boston, USA Nelson Villarroel, MD Insert your Photo Live Global Breast Cancer Tumor Board 3 Apr 2017

14 Case 2 – Quito  Woman from Quito, Ecuador  PMH: Breast Cancer dx in 1998: Received right quadrantecomy + axillary dissection + FAC + RT + Tamoxifen (19 yrs ago)  No F/H of cancer, no HRT, no OCP  Q2 2013: Skin nodules in the Left breast + BL mass present on US  Core Biopsy and skin biopsy: Invasive Ductal Carcinoma G1, Well differentiated IHC: R breast ER 95% PR 1% HER2 +ve, ki67: 49% L breast ER 92% PR 60% HER2 +ve, ki67: 69%

15 Case 2 – Quito  Q2 2013: Whole body CT scan: BL breast masses – otherwise NED Bone Scan: Negative PET CT: R Breast 5.9 suv and Left 3 suv, Hypermetabolic + axillary and mediastinal lymph nodes

16 Case 2 – Quito Q2 2013: Started TCH x 6 cycles until Q3 2013 Q4 2013: L breast salvage mastectomy HP: Several microscopic foci no vascular or lymphatic infiltration + one positive lymph node Q4 2013: Tumor board: Salvage mastectomy (no microscopic evidence of tumor) and RT (not a candidate) Q1 2014: Started Exemestane and adjuvant Trastuzumab. Completed 18 cycles of chemo Q1 2015 negative CT Scan ( follow up) Diagnosis: Left Breast Cancer Stage IIIB

17 Case 2 – Quito  Q3 2015 PE: 2 skin Nodules - L chest wall  Q4 2015 Skin Biopsy: Metastatic Ductal carcinoma ER 88%, PR-ve, HER2 +ve  Q4 2015: CT scan: 5 lymph nodes up to 20 mm, L axilla Bone Scan -ve  Q4 2015 Tumor board gave 3 options: T-DM1, Trastuzumab, or capecitabine + lapatinib and T-DM1 was chosen  Q4 2015: Started Trastuzumab + Paclitaxel (T-DM1 took time - was not approved)

18 Case 2 – Quito  Q1 2016: CT scan after 3 cycles of chemo - no evidence of axillary lymph nodes - completed 6 cycles by Q2 2016  Q2 2016: New skin lesions on the chest Biopsy: moderately differentiated ductal carcinoma ER 95%, PR 24%, KI67 47%, HER2 +ve with Negative CT scan  Q2 2016: EF 59% (was 67%), started Letrozole and Zometa due to Osteopenia  Q3 2016: CT scan 22 and 23 mm L axillary lymph nodes and 4 skin nodular lesions up to 19 mm on the chest with 2 more around the Xiphoid

19 Case 2 – Quito  Q3 2016: Positive biopsy. Started LAPATINIB/ CAPECITABINE  Q1 2017: CT scan: Complete response of lesions by cycle 5  Q2 2017: New skin lesions, biopsy - negative  Q2 2017: On Lapatinib/Capecitabine and pending new CT scan, Karnofsky 90%, ECOG 1

20  ? What to do next if we have new metastatic skin or bone lesions  ? What is the prognosis of this patient  ? Should she receive Fulvestrant next She was previously treated with tamoxifen, letrozole and exemestane Case 2 – Quito Questions and Discussion:

21 Lviv, Ukraine Boston, USA Taras Tsolko MD Insert your Photo Live Global Breast Cancer Tumor Board 3 Apr 2017

22 Case 3 – Lviv  48 y/o post-menopausal woman with palpable R breast mass No co-morbidities Home maker F/H: father with laryngeal cancer

23 Case 3 – Lviv  1994: first reported symptoms of discomfort in R breast  P/E: 3cm breast mass R inner quadrant; without clinical LN  Imaging: CT chest and R breast: 3.6 x 3.2 cm mass + negative LNs  Biopsy: Invasive carcinoma G3

24 Case 3 – Lviv  Q4 1994: Received 40gy pre - operative RT Right Mastectomy (Patey) + radical ALND Histology: Invasive carcinoma G3, in all lymph nodes, immunology - no mets Diagnosis: Stage IIa R breast cancer (T2, N0, M0)

25 Case 3 – Lviv  Q4 1994: 3 x CMF (cyclophosphamide, methotrexate, and 5FU) After 3 cycles, refusal of further treatment 2016: Ultrasound - ovarian tumor Q3 2016 CT: R ovarian tumor - mets in pelvic node Q3 2016: Laparoscopic hysterectomy with ALN dissection Histology: Mets non differentiated ductal carcinoma from breast ER 30% (+ve), PR (-ve), Her 2 neu (-ve)

26 Case 3 – Lviv  Q3 2016: BRCA1 – 493insT  Q1 2017: New subcutaneous mets  Q1 2017: Veliparib 120 mg b.i.d + paclitaxel 128 mg (1+8+15) + carboplatinum 516 mg (1), every 22days

27  ? 23 years from her first operation - Is this the same cancer  ? Should we find a new breast tumor  ? Further therapy  ? Should we have started with a biopsy instead of hysterectomy Case 3 – Lviv Questions and Discussion: