1. 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)

2. 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

3. 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

4. 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

5. 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

6. 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)

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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+

14. 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

15. 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

16. 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
Yip CH, et al. World J Surg 2015; 39:
Tomás Reinert, et al. Rev. Bras. Ginecol. Obstet. vol.38 no.12 Rio de Janeiro Dec
Torre LA, et al. CA Cancer J Clin. 2015; 65(2):
Smith IE et al. N Engl J Med 2003; 348:
Ellis MJ et al. Breast. Cancer Res Treat :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 ,
Eiermann W, et al. Ann Oncol. 2001; 12(11):
Regan MM et al. BIG 1-98 Collaborative Group; International Breast Cancer Study Group (IBCSG)

17. CHLO - Breast Cancer Unit team

18. Thank you for your attention
Vasco Fonseca, MD