Breast Cancer Update 2014 Prevention, Risk, and Treatment of Early Stage Breast Cancer. Kevin R. Fox, MD University of Pennsylvania

Transcription

1 Breast Cancer Update 2014 Prevention, Risk, and Treatment of Early Stage Breast Cancer Kevin R. Fox, MD University of Pennsylvania

2 Prevention of Breast Cancer

3 Accepted treatments Tamoxifen (premenopausal women) Raloxifene (postmenopausal women) Exemestane (postmenopausal women)

4 First results of the International breast cancer intervention study II (IBIS II): a multicentre prevention trial of anastrozole versus placebo in postmenopasual women at increased risk of developing breast cancer Kusick et al., SABCS 2013 Abstract S3-01

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11 Fertility treatments: do they increase the risk of breast cancer?

12 Breast cancer incidence after hormonal infertility treatments: Systematic review and meta-analysis of population based studies Gennari et al., SABCS 2013 Abstract S5-08

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17 Adjuvant Treatment of Early Stage Breast Cancer

18 Treatment Choices Chemotherapy Endocrine therapy (tamoxifen, anastrozole et al. ) Trastuzumab (Herceptin) Radiation therapy

19 Tamoxifen- how long?

20 ATLAS- 10 v 5 years of adjuvant tamoxifen (TAM) in ER+ disease: effects on outcome in the first and in the second decade after diagnosis Davies, C. et al. SABCS Abstract S1-2

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24 Trial Design of MA.17 Randomization (All patients disease-free) Tamoxifen 0 3 Letrozole 2.5 mg qd* months n=2575 Placebo qd n=2582 Approx. 5 years adjuvant 5 years extended adjuvant Primary end point: DFS Secondary end points: OS/safety/QOL Substudies: BMD/bone markers, lipid profile *n=2575 (efficacy), 2154 (safety); n=2582 (efficacy), 2145 (safety). QOL = quality of life; BMD = bone mineral density. Goss et al. N Engl J Med. 2003;349:1793.

25 Dealing with side effects

26 Randomized trial of exercise vs. usual care on aromatase inhibitor-associated arthalgias in woman with breast cancer: The hormones and physical exercise (HOPE) study Irwin, et al. SABCS 2013 Abstract S03-03

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32 Treatment of HER-2 positive early stage breast cancer

33 Basic concepts All breast cancers have some HER2 Some (20%) have too much These cancers can be bad behavers Trastuzumab corrects this Chemotherapy is required as well

34 A phase II study of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2 positive breast cancer (BC) Tolaney et al., SABCS 2013 Abstract S01-04

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37 Preoperative or Neoadjuvant Chemotherapy

38 Indications Inoperable cancers Inflammatory cancers Cancers for which surgery would be difficult Large cancers with intent to make them smaller for lumpectomy

39 Goals of treatment Maximum shrinkage of the tumor Over 90% of cancers shrink somewhat About 30-40% shrink completely, but When surgery is then performed, most patients will still have evidence of cancer in the breast Some cancers disappear completely and when surgery is performed, all evidence of cancer is gone This is called a pathological complete response

40 Preoperative chemotherapy for patients with HER2 positive breast cancer

41 NEOSPHERE * Phase II pcr Rates in 4 Combinations of Trastuzumab, Pertuzumab, Docetaxel in Operable, Locally Advanced, or Inflammatory EBC: Study Design Patients with operable or locally advanced/ inflammatory a HER2-positive BC Chemotherapy-naïve and primary tumors >2 cm TH (n=107) Docetaxel + trastuzumab THP (n=107) Docetaxel + trastuzumab + pertuzumab HP (n=107) Trastuzumab + pertuzumab S U R G E R FEC q3w 3 Trastuzumab q3w cycles 5-17 FEC q3w 3 Trastuzumab q3w cycles 5-17 Docetaxel q3w 4 FEC q3w 3 Trastuzumab q3w cycles 5-17 (N=417) TP (n=96) Docetaxel + pertuzumab Y FEC q3w 3 Trastuzumab q3w cycles 5-21 Study dosing: q3w 4 RT and standard hormone treatment for ER-positive patients were prescribed per local guidelines a Locally advanced=t2 or T3, N2 or N3, M0 or T4a-c, any N, M0; operable=t2 or T3, N0 or N1, M0; inflammatory=t4d, any N, M0 EBC=early-stage breast cancer; FEC=5-fluorouracil, epirubicin and cyclophosphamide; pcr=pathologic complete response Gianni L, et al. Lancet Oncol 2012;13:25. M2.P.BC.Early.Ow.29 *Genentech/Roche Sponsored Study

42 NEOSPHERE * Phase II pcr Rates in 4 Combinations of Trastuzumab, Pertuzumab, Docetaxel in Operable, Locally Advanced, or Inflammatory EBC: pcr and Hormone Receptor Status ER or PR positive ER and PR negative pcr, % ± 95% CI TH THP HP TP Treatment EBC=early-stage breast cancer; ER=estrogen receptor; H=trastuzumab; P=pertuzumab; pcr=pathologic complete response; PR=progesterone receptor; T=docetaxel Gianni L, et al. Lancet Oncol 2012;13:25. M2.P.BC.Early.Ow.34 *Genentech/Roche Sponsored Study

43 TRYPHAENA * Phase II Neoadjuvant Trastuzumab and Pertuzumab in HER2-Positive EBC: Study Design Cycles A FEC Docetaxel HER2-positive EBC, centrally confirmed (n=225) B C FEC Pertuzumab + trastuzumab Docetaxel Docetaxel Pertuzumab + trastuzumab Pertuzumab + trastuzumab S U R G E R Y Trastuzumab to complete 1 year Carboplatin All 3 arms were experimental Stratification: Operable, locally advanced, and Study dosing q3w: inflammatory breast cancer FEC: 500 mg/m 2, 100 mg/m 2, 600 mg/m 2 Hormone receptor positivity Carboplatin: AUC 6 Trastuzumab: 8 mg/kg loading dose, 6 mg/kg maintenance Pertuzumab: 840 mg loading dose, 420 mg maintenance Docetaxel: 75 mg/m 2 (escalating to 100 mg/m 2 if tolerated, in Arms A and B only) EBC=early-stage breast cancer; FEC=5-fluorouracil, epirubicin, cyclophosphamide Schneeweiss A, et al. Ann Oncol. 2013;24(9): M2.P.BC.Early.Ow.59 *Genentech/Roche Sponsored Study

44 TRYPHAENA * Phase II Neoadjuvant Trastuzumab and Pertuzumab in HER2-Positive EBC: Pathologic Complete Response (pcr) by Hormone Receptor Status 100 ER and PR negative ER and/or PR positive Pathologic Complete Response (ypt0/is), % FEC + HP 3 THP 3 (n=73) FEC 3 THP 3 (n=75) TCH + P 6 (n=77) 50.0 C=carboplatin; EBC=early-stage breast cancer; ER=estrogen receptor; FEC=5-fluorouracil, epirubicin, cyclophosphamide; H=trastuzumab; P=pertuzumab; PR=progesterone receptor; T=docetaxel Adapted from Schneeweiss A, et al. Ann Oncol. 2013;24(9): M2.P.BC.Early.Ow.69 *Genentech/Roche Sponsored Study

45 Conclusions in 2014 Chemoprevention - reasonable or not? Are fertility treatments safe? Tamoxifen for ten years- not so fast Exercise is good for you! HER2-positive breast cancer- does everyone need chemotherapy too?

46 Thanks