NEOADJUVANT THERAPY FOR BREAST CANCER: LOCAL EXPERT OPINION AND RECENT EVIDENCE Dr. Joanne Chiu Medical Oncology Queen Mary Hospital The University of Hong Kong
HONG KONG SURVEY FOR NEOADJUVANT THERAPY IN BREAST CANCER The treatment of breast cancer has revolutionized in the past ten years Statistics demonstrate an increasing adaptation of pre-operative therapy for localized breast cancer A survey was conducted amongst local high-volume centres and doctors as a fact finding exercise on local practice in neoadjuvant therapy for breast cancer 1. Patient selection 2. Logistic 3. Choice of neoadjuvant therapy 4. Post treatment issue: pcr intrepretation, IHC status, LN management
Number HONG KONG SURVEY RESULTS 80 65 respondents (55% responded) Breakdown by specialty: 70 60 38 oncologists (73 invited) 50 22 surgeons (36 invited) 40 4 pathologist (11 invited) 1 radiologist (7 invited) 30 20 Invited Responded Breakdown by setting: 34 in public hospitals 20 in private clinics 10 0 Oncologists Surgeons Pathologists Radiologists 11 in private hospitals Specialty Majority of respondents noticed an increase trend in use of neoadjuvant therapy in the last 5 years, and they considered the neoadjuvant therapy to be a standard of care
PATIENT SELECTION WOULD YOU RECOMMEND NEOADJUVANT THERAPY FOR LOCALLY ADVANCED (T>2 AND N<1) BUT STILL OPERABLE BREAST CANCER? 3% 8% Agreed that neoadjuvant therapy should be considered for downsizing in operable breast cancer patients who wants BCT 89%
DO YOU HAVE AN UPPER-AGE LIMIT FOR RECOMMENDING NEOADJUVANT THERAPY? 8% 54% 38% Biological age, and the presence of comorbidities would probably be more important consideration than actual age for offering neoadjuvant therapy Choice of neoadjuvant therapy is subtype-dependent Some regimens can be chemotherapy-free Neoadjuvant therapy is very effective in certain subtypes of breast cancer.
LOGISTIC DO YOU PRACTICE IN AN INSTITUTION WITH A DEDICATED BREAST CANCER MULTIDISCIPLINARY TEAM (MDT)? 32% 68% MDT plays a crucial role in the management of early breast cancer. It is the current gold standard of management as recommended by various guidelines 1,2 1. http://www.dh.gov.uk/publications 2. NICE guidline, updated 2017 Public: 100% Private: 39% Many private doctors have solo practice Coordination of MDT requires dedicated leaders & concerted commitment of all team members Private doctors might not have enough patient volume for a particular cancer to justify MDT
IS THERE A DEDICATED CASE MANAGER RESPONSIBLE FOR THE COORDINATION OF NEOADJUVANT CHEMOTHERAPY FOR TIMELY TREATMENT AND SUBSEQUENT ASSESSMENT TO ENABLE A SMOOTH PATIENT JOURNEY IN THIS COMPLEX LOGISTICAL TREATMENT PARADIGM? Role of case manager has been defined: Liaise for and follow the progress of the patient from diagnosis to surgery 43% 57% Public: 97% Private: 19% Under HA COC cancer, each breast cancer patient is required to have a case manager.
DO YOU ROUTINELY DISCUSS THE USE OF NEOADJUVANT THERAPY IN MDT MEETINGS BEFORE THE COMMENCEMENT OF THERAPY? Oversea experience and recommendation: 35% 8% 57% Public: 70% Private: 43% Retrospective studies suggested implementation of MDT was associated with better patient survival 1,2 Regional guidelines to govern the structure and running of MDTs has been suggested by international guideline 3 Encourage interdisciplinary team discussion wherever possible, or liaise with centers with MDT board Although an MDT is available, only selected cases are discussed before the commencement of neoadjuvant therapy The effectiveness, expertise, and actual utilization of MDT in each center remained unclear 1. Eaker et al., Cancer Epidemiol biomarkers Prev, 2005; 2. Kesson et l., BMJ, 2012; 3. NICE guidline 2002
WHAT IS THE PREFERRED METHOD FOR STAGING BEFORE STARTING NEOADJUVANT THERAPY? 40 35 30 25 20 15 10 5 0 46% 58% Expert preference: PET-CT/MRI is the preferred method of staging, yet not included in most guidelines Good specificity in axilla evaluation Better than CT in detection of N3 disease and distant metastasis Systemic imaging should be encouraged in all node-positive disease CT is acceptable if patients cannot afford PET
IS THE INSERTION OF A METALLIC MARKER IN THE TUMOUR BED BEFORE STARTING NEOADJUVANT THERAPY A ROUTINE PRACTICE IN YOUR INSTITUTION? 44% 10% 46% Marker insertion prior to commencement of neoadjuvant therapy should be a standard practice => put forward in specialty surgical forum Omission of marker in patients receiving neoadjuvant chemotherapy and BCT was associated with increased local recurrence 1,2 Marker insertion, even for planned mastectomy can facility pathological evaluation 1. Oh et al., Cancer, 2007; 2. Dash et al., AJR Am J Roentgenol, 1999
CHOICE OF NEOADJUVANT THERAPY
HER2-positive breast cancer FOR HER2+ BREAST CANCER PATIENTS BEING OFFERED NEOADJUVANT THERAPY, IS DUAL BLOCKADE WITH TWO ANTI-HER2 AGENTS AN APPROACH YOU CONSIDER PART OF YOUR PRACTICE? 21% 11% 68% Double anti-her2 blockade should be offered where possible NeoSphere: Trastuzumab + pertuzumab with chemotherapy increased pcr which translated into reduction in recurrence 1 1. Gianni etla., Lancet Oncol, 2016
DO YOU CONSIDER ANTHRACYCLINES AN ESSENTIAL COMPONENT OF THE CHEMOTHERAPY BACKBONE IN TREATMENT OF HER2 + BREAST CANCER IN THE NEOADJUVANT SETTING? 22% 54% 24% Perhaps with the great response rate of modern double anti-her2 regimen, the use of anthracycline should be diminished BCIRG006 1 : high risk HER2-positive patients given AC + TH c/w DCH had 5x CHF and increased leukemia APHINITY 2 and NeoSphere 3 improved survival and pcr with adding pertuzumab The role of anthracycline is unclear for patients with resistant or residual disease 1. Slamon et al., Cancer Res, 2016 2. Von Minckwitz et al., NEJM, 2017 3. Gianni etla., Lancet Oncol, 2016
Hormone-receptor positive HER2-negative breast cancer FOR POST MENOPAUSAL HR+ HER2 BREAST CANCER PATIENTS, IS NEOADJUVANT THERAPY WITH AN AROMATASE INHIBITOR (AI) A POSSIBLE RECOMMENDATION FOR YOU? 10% 3% Neoadjuvant AI in post-menopausal women with luminal A disease is a well accepted option St. Gallen consensus: favors de-escalation from chemotherapy 1 87% Genomic testing can provide guidance on patients who don t derive additional benefit with chemotherapy Early data for node-positive disease Enrolling into clinical trial is an acceptable option 1. Gnant et al., Breast Care, 2017
Triple negative breast cancer FOR PATIENTS WITH TRIPLE-NEGATIVE BREAST CANCER RECEIVING NEOADJUVANT THERAPY, WOULD YOU ROUTINELY INCORPORATE PLATINUM SALTS, SUCH AS CISPLATIN OR CARBOPLATIN, INTO THE REGIMEN? consensus can be reached 21% Some evidence to suggest use of carboplatin is associated with modest increase in pcr but more toxicity 44% Use in BRCA+ disease: inadequate data 35%
WOULD YOU CONSIDER TESTING FOR BRCA MUTATIONS OR OTHER INHERITABLE GENETIC PREDISPOSITIONS TO BREAST CANCER FOR TRIPLE-NEGATIVE BREAST CANCER PATIENTS DURING NEOADJUVANT THERAPY? BRCA status can provide guidance on choice of surgery 24% Turnaround time limits how it can impact decision making 41% 35%
Pathological outcome WOULD YOU AGREE WITH THE STATEMENT PATHOLOGICAL COMPLETE RESPONSE (PCR) AT SURGERY IS PROGNOSTIC OF EVENTUAL CLINICAL OUTCOME FOR A SUBGROUP OF BREAST CANCER PATIENTS UNDERGOING NEOADJUVANT THERAPY? 1% 2% 97% HR+/HER2 - HER+/HER2+ HR-/HER2+ TNBC
FOR PATIENTS WITH RESIDUAL INVASIVE CANCER AFTER NAC, IS ER/PR AND HER2 IMMUNOHISTOCHEMISTRY (IHC) PERFORMED ROUTINELY? 18% 82% IHC on residual invasive cancer should be done routinely It can affect management Most respondents had experience with change in subtype in residual tumor 23% 5% 13% 59% Less than 5% of the time 5-10% of the time 10-30% of the time More than 30% of the time
Sentinel lymph node WOULD YOU CONSIDER PERFORMING SENTINEL NODE BIOPSY FOR PATIENTS AFTER NAC IF THEIR PRETREATMENT NODAL STATUS IS NEGATIVE? 14% 3% It is a standard practice 1,2 83% 1. NCCN guideline 2018 2. Lyman, JCO, 2015
WOULD YOU CONSIDER PERFORMING SENTINEL NODE BIOPSY FOR PATIENTS AFTER NAC IF THEIR PRETREATMENT NODAL STATUS IS POSITIVE BUT THEIR POST-NAC PET SCAN SHOWED METABOLIC QUIESCENCE (CN1/2 => CN0)? 43% 8% 49% Management in such situation is still controversial 1 San Gallen consensus 2 : SNB is the gold standard with negative axillary staging after neoadj therapy; while axillary clearance is still recommended with at least 1 metastatic node found Patients with limited SLN+, SLND or ALND had similar surival 3 Role of adjuvant RT in this case? 1. Corso et al., Future Med, 2018 2. Gnant et al., Breast Care, 2017 3. Giuliano et al., JAMA, 2017
SUMMARY Neoadjuvant therapy for early breast cancer is a standard of care, and should be considered for patient being considered for BCT MDT plays a crucial role in the management in these patients Systemic imaging should be done in all LN+ disease Choice of neoadjuvant regimen: Double anti-her2 with pertuzumab/trastuzumab Hormonal therapy for post-menopausal luminal A Role of platinum in TNBC still controversial IHC for residual disease should be performed routinely SLN post-neoadjuvant therapy is a gold standard. Who should get ALND / adj RT is still controversial
Acknowledgment Dr. CHAN Keeng Wai Dr. Polly CHEUNG Dr. Joanne CHIU Dr. Carol KWOK Dr. Ava KWONG Dr. Roland LEUNG Dr. Lawrence LI Dr. NG Ting Ying Prof. Roger NGAN Dr. Inda SOONG Dr. SUEN To Ki Dacita Dr. WONG Ting Ting Dr. Thomas YAU Prof. Winnie YEO May Lee