ABSTRACT
Introduction During the coronavirus 2019 (COVID-19) pandemic in USA, NET use has been recommended to allowsafe deferral of surgical treatment in early stage, estrogen receptor positive breast cancer (ER+BC). In suchcircumstances, after NET use there is limited guidance on locoregional treatment, especially with management of the axilla. We aimed to evaluate patterns of care in early stage ER+BC during the first several months of theCOVID-19 pandemic. Method A cross-sectional, 30-item survey was developed using a standardized surveydevelopment framework. The survey was administered May 8 - June 12, 2020 to a convenience sample of medicaloncologists (MO), radiation oncologists (RO), and surgeons (SO) - breast committee members of two nationalcooperative groups (Alliance and SWOG) with additional participation through chain referrals. Providers were presented with general questions on NET use before and during the pandemic. They were asked their propensity foromitting axillary lymph node dissection (ALND) after NET if 1 micrometastatic node is found on sentinel lymph nodebiopsy, based on duration of NET. Results 114 providers from 29 US states completed the survey - 42 (37%) MO, 14(12%) RO, and 58 (51%) SO, the majority (N=73/96, 76%) with practices dedicated ≥ 75% to BC, at NCI designatedcomprehensive cancer centers 52% (N=48/94) and in large cities (N=49/94, 52%). Prior to COVID-19, most rarely(N=49/107, 46%) or sometimes (N=36, 33%) used NET for early stage ER+BC. Nearly half were willing to delay.surgery up to 2 months (46%) and 3 months (21%) without use of NET (Table 1, p<0.05). Most providers wouldperform a genomic assay on the biopsy specimen on all or select patients prior to NET initiation, more frequently byMO compared to RO and SO (90% vs. 75% and 60%, p<0.05). The most preferred regimen was tamoxifen (withoutovarian suppression) for premenopausal patients and aromatase inhibitor for postmenopausal patients. Mostplanned to use NET for as little time as possible until surgery could proceed. When stratified by specialty, more MOstated they would vary the duration of therapy based on patient's risk of cancer progression. Most providersrecommended omitting ALND after 1, 2, or 3 months of NET (1 month N=56/93, 60%;2 months N=54/92, 59%;3months N=48/90, 53%). With longer duration of therapy, the propensity for omitting ALND decreased (definitely omitafter 6 months N=25/91, 27%;probably omit after 6 months N=38/91, 42%;definitely omit after 1 year N=26/92,28%;probably omit after 1 year N=29/92, 32%). Omitting ALND was not associated with provider's years in practice,percent of practice dedicated to BC, practice type or setting, participation in multidisciplinary tumor board, or numberof COVID-19 cases in the provider's practicing state. ConclusionMost providers changed their management of early stage ER+BC during the COVID-19 pandemic by utilizing NET until surgery could proceed. As the duration of NET extended, more providers favored ALND in low volume axillary metastatic disease in early stage ER+BC.Additional data to inform the care on post-NET locoregional management is needed.
ABSTRACT
Background: NET is offered to postmenopausal patients (pts) with clinical stage 2/3 ER+/HER2- BC to promotebreast-conserving surgery. Also limited surgical accessibility during the COVID19 pandemic has increased NETutility. Inability to identify ET-resistant disease at diagnosis risks disease progression (PD) and delays more effectivetreatments. Dowsett et al. recently demonstrated that baseline levels of ER, progesterone receptor (PR), Ki67(>15% vs ≤15%), and Ki67 (>10% vs ≤10%) 2-4 weeks (wks) after starting NET may improve appropriate patient(pt) selection for NET (PMC7280290). The ER, PR and Ki67-based prediction model divides pts with primaryER+/HER2- BC into 3 groups for appropriateness for NET: (Group 1) NET is likely to be inappropriate (Allred ER <6or ER 6 and PgR <6), (Group 2) NET may be appropriate and a biopsy for on-treatment Ki67 analysis may beconsidered after 2-4 wks of NET (2A: ER 7 or 8 and PgR <6 and 2B: ER 6 or 7 and PgR ≥6) given that on-treatment Ki67 >10% has been associated with worse outcome (PMC5455353), or (Group 3) NET is appropriate (ER 8 andPgR ≥6). The ALTERNATE trial ( NCT01953588 ) randomized postmenopausal women with clinical stage II or III,ER+ (Allred score 6-8)/HER2- BC to receive anastrozole (ANA), fulvestrant (FUL), or ANA + FUL for 6 months,unless Ki67 was >10% on wk 4 or 12 biopsy, in which case pts were triaged to receive neoadjuvant chemotherapy(NCT) or surgery. As previously reported, the ET-sensitive disease (mPEPI 0 plus pCR) rates were similar acrossthe treatment arms and overall 22% (286 of 1,299) pts had Ki67 >10% at wk 4 or 12. The ALTERNATE trialtherefore provides a large independent data set to evaluate the NET appropriateness model. Results: Among 1,299 eligible pts randomized to receive 6 months of NET, 214 were excluded due to absent HRAllred score (n=41) or absence of pre-treatment and wk 4 Ki67 determinations (n=173). The proportions of theremaining 1,085 pts in Group 1, 2 and 3 were 1% (n=10), 43% (n= 468), and 56% (n=607), respectively. On-studyKi67 >10% prompting conversion from NET to NCT/Surgery occurred in: Group 1 90% (9 of 10), Group 2 30% (141of 468), and Group 3 17% (104 of 607) ( Table 1 ). Among the 1,075 pts in Groups 2 and 3, 260 (24%) pts had Ki67≤15% at baseline (BL), among whom only 14 (5.4%) had Ki67 >10% at wk 4, compared to 231 of the 815 (28.3%)who had BL Ki67 >15% and subsequent Ki67 >10% at wk 4. 2% of pts who remained on NET due to on-treatmentKi67 <10% had PD. Response and PEPI-0 rates by group will be reported. Conclusion: ALTERNATE trial data support a model whereby levels of ER, PR and Ki67 at diagnosis can be usedfor the identification of postmenopausal pts with primary ER+/HER2- BC who are appropriate for NET. Whenbaseline ER Allred scores are >6 and Ki67 ≤15%, there is a low likelihood of ET-resistant disease. When BL Ki67 is>15%, ET sensitivity is variable, and on-treatment biopsy for Ki67 may assist in triaging regarding NETappropriateness, particularly given the extremely low local PD rates seen in ALTERNATE when on-treatment Ki67was <10%. (Table Presented).