Speaker: Vasco Fonseca (Medical Oncologist) 19th Euro Congress on Cancer Science and Therapy & 25th Cancer Nursing & Nurse Practitioners Conference July 17-19, 2017 Lisbon, Portugal Speaker: Vasco Fonseca (Medical Oncologist)

Do Breast Cancer Units treat patients based on their own neoadjuvant protocols? Vasco Fonseca, Zacharoula Sidiropoulou Breast Unit, Centro Hospitalar Lisboa Ocidental (CHLO), Lisbon, Portugal

Summary 1 – Presenting our Breast Cancer Unit 2 – The need of a Neoadjuvant Breast Cancer protocol 3 – HOTBREAST trial 3 – Expected outcomes Impact on clinical practice Clinical recommendations 4 – Final remarks

Our Breast Cancer Unit CHLO incorporates 3 hospitals + 1: Hospital de Egas Moniz Hospital de Santa Cruz Hospital São Francisco Xavier (Hospital de Cascais) We treat almost 300 new breast cancer patients per year After an internal audit, we observed that the patients allocated to neoadjuvant treatment are few in number

Breast cancer - Neoadjuvant treatment protocol - trials Aim at improving clinical practice, both in developed and underdeveloped regions Aim at improving auditing - collected data may contribute to improve global healthcare Clinical trials in the neoadjuvant setting allow new drugs to be tested in a more suitable way

Why such a protocol? International guidelines are clear BUT In the “grey area” the experience of the centre matters, so we assess tumor staging tumor biology patient’s preferences individual risk factors relative contraindications and we take these factors under consideration for the neoadjuvant treatment decision (according to international data)

neoadjuvant treatment Neoadjuvant Protocol includes all indicated patients compiles a database for their follow-up triple negative, Her2 positive tumors and Luminal B-like with high proliferative index, equal or above 2 cm (cT2N0) Patients with hormone dependent tumors that refuse surgical treatment, older patients, or patients with severe comorbidities, as well as selected Luminal-A-like patients neoadjuvant treatment Neoadjuvant hormonal treatment

HOT BREAST Trial Included: selected females aged >50y, and after a biopsy of Luminal-like Breast Cancer will go under aromatase inhibitor, from the diagnosis day till the surgical therapy to be decided (if so) patients that refuse surgical treatment are also included, remaining this way in an "active surveillance" Authors argue that introducing early endocrine therapy is a valid option and should be considered under clinical guidelines

HOT BREAST Trial – Hypothesis This approach influences the tumor biology and the surgical approach This approach influences tumor pathologic response and progression free survival It is a valid approach, for patients with poor performance status or that refuse surgical treatment

Relevant details (Neoadjuvant protocol) High risk patients are studied for BRCA1/2 mutation during neoadjuvant chemotherapy: chemotherapy regimen will be adapted or subsequent surgical will be the option All neoadjuvant protocol patients are staged with Torax-abdominal-pelvic Computer Tomography (CT), Bone scan In some cases: Positron Emission-CT Some Her2 positive patients also undergo a Head-CT or Head-MRI moreover, patients are referred to another centre (IPO) for timely assessment of genetic and familiar risk factors

Relevant details (Neoadjuvant protocol) Exames de Estadiamento Relevant details (Neoadjuvant protocol) Examinations to define staging – in the case of tumors cT2 ( ≥ 2.1cm), triple negatives and N+: Bone scan (Skeletal scintigraphy); Thorax radiography/ TC Thorax; abdominal echography PET-TC in case of doubt particularly in advanced stages of localized tumors or in the presence of metastasis Difficult and suspect cases: axillary lymph node study with clinical and imaging evaluation (by ultrasound) is indicated for histological confirmation. The primary lesion should always be marked with clips before the start of neoadjuvant treatment Neoadjuvant hormone therapy as therapeutic option for patients with poor general condition and those whom refuse surgery After completion of the neoadjuvant regimen, a new imaging evaluation of the primary lesion should be performed - Mammary Resonance

Relevant details (Neoadjuvant protocol) Exames de Estadiamento Relevant details (Neoadjuvant protocol) If initial N0 is observed - sentinel node biopsy is performed during the surgical procedure If initial N+ is observed - axillary lymph node dissection RGFTU Protocol includes patients who meet the family risk referral criteria The patients expected to have the greatest benefit from neoadjuvant hormone therapy will be those with luminal A and or lobular tumors; the use of Aromatase Inhibitors should be the preferred option in patients undergoing neoadjuvant hormone treatment Neoadjuvant chemotherapy should include chemotherapy regimens with sequentially administered Anthracyclines and Taxanes

To be considered CT / Platinum in context of neoadjuvancy is particularly indicated for patients with mutations in the BRCA1 or BRCA2 genes Dose-dense regimen show higher Complete Pathological Response in the case of patients with triple negative and premenopausal tumors Adjuvant treatment with fluorouracil (Create X Trial) or metronomic CT ( CTX and MTX / IBCSG Trial 22); after neoadjuvant CT The Create X clinical trial showed increased Global Survival and increased disease-free lifetime. This option should be considered primarily for patients with negative hormone receptors Neoadjuvant CT with Pertuzumab and Transtuzumab (NeoSphere Trial) showed an increase in the pathological response rates. This option should be evaluated in patients with overexpression of CERB 3+

Outcomes Our protocol allows the registry of data every three months data collection for prospective follow up continuous influx of information that allows us to review the therapeutic strategy

Expected advantages of the neoadjuvant protocol To collect and organize data in order to support future actions and decisions Facilitates auditing Observation, registration and identification of the causes for time delays that occur from diagnosis until treatment Assessment of the effects of new drugs is facilitated under neoadjuvant treatment protocols To improve clinical practice at our unit (and eventually extend to others) Useful tool for all Breast cancer units

References Bleicher RJ, et al. JAMA Oncol 2016; 2:330-39. ESMO, European Society for Medical Oncology. ESMO Clinical Practice Guidelines: Breast Cancer. Available at http://www.esmo.org/Guidelines/Breast-Cancer. Yip CH, et al. World J Surg 2015; 39:686-92.7. Tomás Reinert, et al. Rev. Bras. Ginecol. Obstet. vol.38 no.12 Rio de Janeiro Dec. 2016. Torre LA, et al. CA Cancer J Clin. 2015; 65(2):87-108. Smith IE et al. N Engl J Med 2003; 348:2431-42 Ellis MJ et al. Breast. Cancer Res Treat 2007. 105:33-43 Cohen AL et al. POWERPIINC (PreOperative Window of Endocrine TheRapy Provides Information to Increase Compliance) trial: Changes in tumor proliferation index and quality of life with 7 days of preoperative tamoxifen. Breast. 2017, 219-223 Eiermann W, et al. Ann Oncol. 2001; 12(11):1527-32. Regan MM et al. BIG 1-98 Collaborative Group; International Breast Cancer Study Group (IBCSG)

CHLO - Breast Cancer Unit team

Thank you for your attention Vasco Fonseca, MD medicinavf@yahoo.com +351-968859773