ESMO Preceptorship Programme Breast Cancer Lisbon 16,17 September 2016 Emanuela Risi Sandro Pitigliani Medical Oncology Department Hospital of Prato, Istituto Toscano Tumori, Prato, Italy A case of a BRCA2-mutated ER+/HER2 breast cancer during pregnancy
CATERINA, 32 y/o, ECOG PS 0 Mother to a 10 month-old boy Family history of ovarian (grandmother) and colon cancer (uncle) Comorbidities: ulcerative recto-colitis, not specifically treated (inactive) July 2012: self-detected left breast mass during breast-feeding; concomitant diagnosis of 3 rd week pregnancy Clinical examination and breast US: 3 cm nodule of the left breast, and at least 2 suspicious left axillary lymph nodes. Clinical stage: ct2 cn1 Tru-cut needle biopsy: infiltrating ductal carcinoma (IDC), G3, ER 90% PR 90% Ki67 35%, HER2 2+, non-amplified by FISH Labs: within normal limits; negative tumor markers (CEA= 4; CA15.3=18) Staging: no evidence of distant metastasis
Surgery 26 July 2012: Left mastectomy, axillary lymph node dissection, concomitant reconstruction with implant Pathology: 3 cm IDC, G3, no vascular invasion, R0; Lymph node macrometastases: 20/23 Stage and disease subtype: pt2 pn3a (20/23) ER 95% PR 95% Ki67 35% HER2 2+, non-amplified by FISH
Which Adjuvant treatment? IDC G3 pt2 pn3a(20/23) ER95% PR 95% Ki67 35% HER2 2+ FISH non-amplified Ongoing pregnancy (1 st trimester) Pre-menopausal state TREATMENT OPTIONS: Chemotherapy CT should be administered after the first trimester of gestation (14-16 weeks) Anthracycline-based regimens (FAC/FEC, AC/EC) Endocrine therapy: contraindicated during pregnancy Aromatase inhibitors + LHRH agonist Tamoxifen +/- LHRH agonist: 5 years 10 years (extended TAM)
Adjuvant Chemotherapy CT-Timing CT-Type Delivery-Timing CT should be administered after the first trimester of gestation (14-16 weeks) Pregnancies where the fetus has been exposed to CT starting in the second trimester should be regarded as high-risk and regular fetal monitoring during gestation should be considered. CT should not be administered beyond week 33 of gestation Anthracycline-based regimens are the most studied during pregnancy and remain the first choice (FAC/FEC, AC/EC) The use of taxanes during pregnancy is endorsed in cases where they are clinically indicated or the use of anthracyclines is contraindicated TREATMENT CHOICE: A 3-week period should be allowed between the last CT dose and the expected date of delivery to avoid delivery during the nadir period Full-term delivery ( 37 weeks) should be targeted whenever possible Peccatori, Ann Oncol 2013 EC x 6 cycles (17/09/2012-02/01/2013) starting from week 14 of gestation Delivery at week 37 of gestation
Adjuvant Endocrine Therapy Premenopausal state, previous adj CT, N+ Clinical recommendation References TAM x 5 years Davies et al, Lancet 2011 TAM x 10 years ATLAS: Davies et al, Lancet 2013 TAM + LHRH agonist SOFT: Francis et al, NEJM 2015 AI + LHRH agonist SOFT-TEXT: Pagani et al, NEJM 2014 ABCSG-12: Gnant et al, Lancet Oncol 2011 TREATMENT CHOICE: TRIPTORELIN 3,75 mg/28 days + TAMOXIFEN 20 mg/day
Surgery Adjuvant treatment Left mastectomy and axillary lymph nodes dissection: pt2 pn3a (20/23) G3 ER 95% PR 95% Ki67 35% HER2 2+, FISH non-amplified ADJ CTx: EC x 6 cycles Childbirth: healthy newborn Genetic test: BRCA2 mut prophylactic right mastectomy: neg ADJ RT: left chest wall + regional lymph nodes ADJ ET: TRIPTORELIN + TAM BC diagnosis Pregnancy diagnosis 14 th w 37 th w Jul 2012 Sep 2012 Jan 2013 Feb 2013 Mar 2013 Apr 2014 Apr 2015
Metastatic disease April 2015: patient presented with cough and dyspnea Lab tests and tumor markers: increased value of CA 15.3 (143); no laboratory alterations. CT scan total body showed multiple lung metastases, pleural effusion, 3 liver lesions (DM max 3 cm), multiple bone osteoblastic metastasis. Bone scan showed increased uptake in spine, pelvis and left femur. STOP TAMOXIFEN, CONTINUE TRIPTORELIN FIRST LINE TREATMENT
Which first line treatment? Almost 3 years DFI Disease progression while on adjuvant ET (2 years) Symptomatic patient Pre-menopausal state BRCA2-mutated TREATMENT OPTIONS: Chemotherapy: Sequential single agents vs combination CT Platinum-based CT Endocrine Therapy Chemotherapy Maintenance Endocrine Therapy
First line treatment Recommendation from the ESO-ESMO ABC-2 panel ET is the preferred option for hormone receptor-positive disease, even in the presence of visceral disease, unless there is concern or proof of endocrine resistance, or there is disease needing a fast response Endocrine treatment after CT (maintenance ET) to maintain benefit is a reasonable option, although this approach has not been assessed in randomized trials Level of evidence IA IC Sequential monotherapy is the preferred choice for MBC. Combination CT should be reserved for patients with rapid clinical progression, lifethreatening visceral metastases, or need for rapid symptom and/or disease control In patients with taxane-naive and anthracycline-resistant MBC or with anthracycline cumulative dose or toxicity (i.e. cardiac) who are being considered for further CT, taxane-based therapy, preferably as a single IA agent, would usually be considered as the treatment of choice. Other options are, however, available and effective, particularly if avoiding alopecia is a priority for the patient. Cardoso F, Ann Oncol 2014 IA
First line Treatment Platinum-based CT in BRCA-mutated MBC Reference Non randomized phase II trial; cisplatin, BRCA1-mut MBC Byrki, Br Can Res 2012 TBCRC 009, phase II trial; Cisplatin or Carboplatin, TNBC (11 pt BRCA1/2 mut) Isakoff, JCO 2015 TNT trial, phase III, Carboplatin vs Docetaxel, TNBC or BRCA1/2-mut Tutt, SABC 2014 phase III trial, Carboplatin + Gemcitabine +/- Iniparib, TNBC O Shaughnessy, JCO 2014 AbbVieM12895 trial: Carboplatin + Paclitaxel +/- Veliparib vs Temozolamide + Veliparib, BRCA1/2-mut REVIVAL trial: Carboplatin + Olaparib vs Capecitabine, BRCA1/2-mut TnAcity trial: NabPaclitaxel + Gemcitabine o Carboplatino vs Gemcitabine + Carboplatin, TNBC ONGOING ONGOING ONGOING - Patient wanted to avoid alopecia TREATMENT CHOICE: CT (Carbolatin-Gemcitabine x 7 cycles) Maintenance ET (MONALEESA-7 trial)
Metastatic treatment CA15.3=143 () CT scan total body: lung, liver, bone (osteoblastic) metastases Bone scan: increased uptake in spine, pelvis, left femur Symptom: dyspnea Lab: normal Almost 3 years DFI STOP TAM Continue TRIPTORELIN 1 line CTx: CARBO-GEM x 7 cycles Maintenance ET: MONALEESA-7 trial TAM or NSAI + goserelin + ribociclib vs TAM or NSAI + goserelin + placebo on adj ET progression (2 years) Apr 2015 Best response: PR after 4 cycles CTx suspended because of myelotoxicity Sep 2015 Best response: SD after 9 cycles Well tolerated without toxicities Oct Treatment is still ongoing 2015
MONALEESA-7 TRIAL
ESMO Preceptorship Programme Breast Cancer Lisbon 16,17 September 2016 Thank you for your attention!