Abstract
BACKGROUND:
In early studies, local recurrence (LR) rates were higher after neoadjuvant chemotherapy (NAC) compared to upfront surgery. Modern outcomes are uncertain, particularly among those who are initially ineligible for breast-conserving surgery (BCSi) and downstage to BCS-eligible (BCSe).
METHODS:
Among patients with cT1-3 breast cancer treated from 2014–2018 who were BCSe after NAC, clinicopathologic characteristics and LR were compared between initially BCSe patients and BCSi patients who downstaged. BCS eligibility was determined prospectively.
RESULTS:
Among 685 patients, 243 (35%) were BCSe pre- and post-NAC and had BCS, 282 (41%) were BCSi pre-NAC, downstaged to BCSe, and had BCS, and 160 (23%) were BCSi pre-NAC, downstaged to BCSe, and chose mastectomy. Median age was 52 years, and most cancers were cT1-2 (84%), cN+ (61%), and HER2+ (38%) or triple-negative (34%). Those who were BCSe pre-NAC had lower cT stage, while those who chose mastectomy were younger (p < 0.05). NAC was usually ACT-based (92%), 99% of HER2+ patients received dual blockade, and 99% of BCS patients received adjuvant radiation. At median follow-up of 35 months, 22 (3.2%) patients developed LR. The Kaplan-Meier 4-year LR rate was not different among groups (1.9% pre- and post-NAC BCSe vs. 6.3% downstaged to BCSe and had BCS vs. 2.7% downstaged and had mastectomy; p = 0.17).
CONCLUSIONS:
LR rates are low after NAC and BCS, even among BCSi patients who downstage, and are not improved in patients who downstage and choose mastectomy. Mastectomy can be safely avoided in BCSi patients who downstage with NAC.
Keywords: breast cancer, chemotherapy, local neoplasm recurrence, mastectomy, breast-conserving surgery
Condensed Abstract/Precis:
In a large cohort (n = 685) of cT1-3 invasive breast cancer patients treated with neoadjuvant chemotherapy (NAC), we investigated whether local recurrence rates were higher in breast conserving-surgery (BCS)-ineligible patients who downstage to BCS compared to those who were initially BCS-eligible and had BCS and those who were BCS-ineligible who downstaged and chose mastectomy. We observed that 4-year local recurrence rates after NAC and BCS were low among those who downstaged (6.3%), and were not improved in patients who chose mastectomy, suggesting that such patients may be safely treated with BCS.
INTRODUCTION
Neoadjuvant chemotherapy (NAC) may be used in operable breast cancer to downstage large primary tumors, permitting breast-conserving surgery (BCS) for many patients who would otherwise require mastectomy. Rates of BCS have increased as NAC has become widely used.1-3 In a consecutive population of 600 patients with large stage I-III tumors initially precluding BCS treated at our institution from 2013 to 2019 with modern NAC, 48% successfully avoided mastectomy, demonstrating a substantial clinical benefit.1
The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) patient-level meta-analysis of 4,756 patients treated in 10 randomized trials of NAC versus adjuvant therapy between 1983 and 2002 similarly demonstrated a higher rate of BCS in NAC patients compared to upfront surgery (65% vs. 49%, P < 0.001).4 However, a higher rate of local recurrence (LR) was observed among those treated with NAC, raising concerns regarding the safety of this approach, particularly among those who downstage to BCS after NAC. This was based upon the observation of a small but statistically significant difference in 10-year LR among those treated with NAC compared to upfront surgery (15.1% vs. 11.9%, P = 0.01).4 The included trials pre-dated targeted systemic therapies and contemporary pathologic, radiologic, and surgical techniques. Rates of LR in patients receiving modern systemic chemotherapy and targeted therapy remain uncertain, particularly in patients who downstage from mastectomy to BCS with NAC. In this cohort of patients treated with modern NAC, we sought to compare rates of LR between those deemed BCS-eligible (BCSe) treated with BCS after chemotherapy,those deemed initially BCS-ineligible (BCSi) who downstaged and underwent BCS, and those who downstaged but chose mastectomy.
MATERIALS AND METHODS
Following Institutional Review Board approval, we identified consecutive patients with cT1-3 invasive breast cancers, as defined in the American Joint Committee on Cancer manual (8th edition),5 treated with NAC from May 2014 to December 2018 from a prospectively maintained, HIPAA-compliant database. This period was selected because it spans sufficient time to allow ≥ 3 years of follow-up following the time at which BCS eligibility began to be recorded in the database. Patients with cT4 disease or multicentric disease who were considered ineligible for downstaging to BCS with NAC, or those who had unknown pre- or post-NAC BCS eligibility were excluded from this analysis. BCS eligibility was prospectively determined by the treating surgeon prior to NAC and at the completion of NAC based upon extent of disease relative to breast size. Three groups were identified for analysis: patients who were BCSe pre- and post-NAC and had BCS, patients who were BCSi pre-NAC, downstaged to BCSe post-NAC, and had BCS, and patients who were BCSi pre-NAC and downstaged to BCSe post-NAC, but chose mastectomy. The latter group was included as a comparator to assess whether resection of the entire original tumor volume in initially BCSi patients would impact LR rate as compared to BCS. The primary outcome of interest was LR, defined as a biopsy-proven in situ or invasive recurrence of the ipsilateral breast or chest wall, with or without disease in the regional lymph nodes, and without any sites of distant disease relapse. Biopsy to confirm LR was performed following detection by examination or imaging abnormality.
Clinicopathologic characteristics were compared between groups using the Wilcoxon rank sum test for continuous variables and chi-square or Fisher’s exact test for categorical variables. Significant covariates from the univariate analysis along with clinical T stage and BCS eligibility group, considered to be important predictors of recurrence regardless of the results of univariate analysis, were then included in the multivariable Cox regression model. Kaplan-Meier methods were used to estimate 4-year LR-free survival estimates by group. Type I error rate was set to 0.05 (α). To account for the 178 patients whose lymphovascular invasion (LVI) status was not reported, we conducted a sensitivity analysis by performing multiple imputation using the mice package in R under the missing at random assumption (MAR). All analyses were performed using R 3.6.3 (R Core Team, 2020).
RESULTS
From May 2014 to December 2018, 1,136 consecutive patients with cT1-3 invasive cancers were treated with NAC; 374 patients were BCSi or had unknown BCS eligibility after NAC and were excluded, as were the 71 patients who were BCSe post-NAC and chose mastectomy and the 6 with unknown BCS eligibility pre-NAC. The remaining 685 patients who were BCSe after NAC comprised the study cohort. Of these, 243 (36%) were BCSe pre- and post-NAC and had BCS, 282 (41%) were BCSi pre-NAC and downstaged to BCSe post-NAC and had BCS, and 160 (23%) were BCSi pre-NAC and downstaged to BCSe post-NAC but chose mastectomy (Fig. 1). All patients underwent pre-treatment mammography, 670 (98%) underwent pre-treatment ultrasound, and 577 (84%) underwent pre-treatment magnetic resonance imaging (MRI). After NAC, 635 (93%) underwent mammography, 165 (24%) underwent ultrasound, and 404 (59%) underwent MRI. The majority of patients received neoadjuvant dose-dense doxorubicin, cyclophosphamide, and a taxane (92%), and 99% of HER2-positive (HER2+) patients received dual targeted HER2 therapy with trastuzumab and pertuzumab. In the adjuvant setting, 216 of 258 (84%) HER2+ patients completed adjuvant trastuzumab and pertuzumab, while the remainder received single-agent HER2 blockade. Most (93%) hormone receptor-positive patients received adjuvant endocrine therapy. Adjuvant radiotherapy (RT) was delivered to 96% of patients who underwent BCS, received by 238 (97.9%) who were BCSe pre- and post-NAC and had BCS, and 267 (94.7%) of BCSi patients who downstaged and had BCS; post-mastectomy RT was delivered to 94 (58.8%) of BCSi patients who downstaged and chose mastectomy. Standard adjuvant RT to the breast or chest wall utilized conventional fractionation to a total dose of 5000 cGy in 25 fractions, or a hypofractionated regimen of 4240 cGy in 16 fractions for BCS patients, at the discretion of the treating physician. A sequential boost to the lumpectomy cavity of 1000 cGy was delivered in 4-5 fractions. Comprehensive nodal irradiation, received by 108 (44.4%) BCSe pre- and post-NAC who had BCS, 105 (37.2%) of BCSi who downstaged and had BCS, and 81 (50.6%) patients who downstaged and chose mastectomy, was delivered to the ipsilateral level I and II axillary nodes, supraclavicular and infraclavicular fossa, and the internal mammary chain in the first three intercostal spaces to a total dose of 5000 cGy in 25 fractions.
Figure 1.
Patient population, categorized by BCS eligibility and choice of surgery. Highlighted boxes indicate study groups.
Abbreviations: BCS, breast-conserving surgery; NAC, neoadjuvant chemotherapy
a. BCS eligibility pre-NAC unknown in 6 cases
b. 22 patients deemed BCS-ineligible post-NAC due to progression of disease, contraindication to radiation, genetic mutation, or other patient factors discovered during NAC
c. BCS eligiblity post-NAC unknown in 1 case
d. One patient pursued BCS despite being categorized as BCS-ineligible
Clinicopathologic characteristics of all patients and each BCS eligibility group are summarized in Table 1. Median age was 52 years, and most cancers were cT1-2 (84%), cN+ (61%), and HER2+ (38%) or triple-negative (34%). Patients who were BCSe pre- and post-NAC and had BCS were older (median age 56 years) compared to BCSi patients who downstaged and had BCS (median age 51 years) or who downstaged and chose mastectomy (median age 44 years, P < 0.001). BCSi patients who downstaged had higher clinical T stage at presentation compared to BCSe patients (P < 0.001) and more often had poorly differentiated tumors (P = 0.04) (Table 1). Breast pathologic complete response (pCR, ypT0) was achieved in 220 (32.1%) patients, and this was similar between groups (P = 0.6).
TABLE 1.
Clinicopathologic Characteristics of the Overall Cohort and Each BCS Eligibility Group
| Characteristic | All patients n = 685 |
Post-NAC BCS-eligible, had BCS |
Pre-NAC BCS- ineligible, downstaged to BCS-eligible, chose mastectomy n = 160 |
P | |
|---|---|---|---|---|---|
| Pre-NAC BCS-eligible n = 243 |
Pre-NAC BCS-ineligible n = 282 |
||||
| Age, years (median, range) | 52 (25–82) | 56 (30–82) | 51 (25–82) | 44 (26–72) | < 0.001 |
| Clinical T stage | < 0.001 | ||||
| 1 | 114 (16.6%) | 82 (33.7%) | 21 (7.4%) | 11 (6.9%) | |
| 2 | 459 (67.0%) | 156 (64.2%) | 200 (70.9%) | 103 (64.4%) | |
| 3 | 112 (16.4%) | 5 (2.1%) | 61 (21.6%) | 46 (28.8%) | |
| Clinical N stage | 0.3 | ||||
| 0 | 267 (39.0%) | 79 (32.5%) | 121 (42.9%) | 67 (41.9%) | |
| 1 | 372 (54.3%) | 145 (59.7%) | 142 (50.4%) | 85 (53.1%) | |
| 2 | 23 (3.4%) | 10 (4.1%) | 9 (3.2%) | 4 (2.5%) | |
| 3 | 23 (3.4%) | 9 (3.7%) | 10 (3.5%) | 4 (2.5%) | |
| Histology | 0.073 | ||||
| Invasive ductal | 645 (94.2%) | 223 (91.8%) | 273 (96.8%) | 149 (93.1%) | |
| Invasive lobular | 33 (4.8%) | 15 (6.2%) | 8 (2.8%) | 10 (6.3%) | |
| Other | 7 (1.0%) | 5 (2.1%) | 1 (0.4%) | 1 (0.6%) | |
| Receptor status | 0.3 | ||||
| ER+/HER2− | 196 (28.6%) | 81 (33.3%) | 70 (24.8%) | 45 (28.1%) | |
| ER+/HER2+ | 164 (23.9%) | 52 (21.4%) | 78 (27.7%) | 34 (21.3%) | |
| ER−/HER2+ | 94 (13.7%) | 30 (12.3%) | 39 (13.8%) | 25 (15.6%) | |
| ER−/HER2− | 231 (33.7%) | 80 (32.9%) | 95 (33.7%) | 56 (35.0%) | |
| Lymphovascular invasion* | 161 (23.5%) | 56 (23.0%) | 61 (21.6%) | 44 (27.5%) | 0.9 |
| Differentiation | 0.04 | ||||
| Well | 6 (0.9%) | 3 (1.2%) | 2 (0.7%) | 1 (0.6%) | |
| Moderate | 167 (24.4%) | 73 (30.0%) | 54 (19.1%) | 40 (25.0%) | |
| Poor | 512 (74.7%) | 167 (68.7%) | 226 (80.1%) | 119 (74.4%) | |
| Breast pCR (ypT0) | 220 (32.1%) | 73 (30.0%) | 92 (32.6%) | 55 (34.4%) | 0.6 |
| Breast pCR (ypT0/Tis) | 272 (39.7%) | 93 (38.3%) | 116 (41.1%) | 63 (39.4%) | 0.8 |
| Final margin status | > 0.9 | ||||
| No tumor | 684 (99.9%) | 243 (100%) | 281 (99.6%) | 160 (100%) | |
| Positive | 1 (0.1%) | 0 (0%) | 1 (0.4%) | 0 (0%) | |
| Developed LR | 22 (3.2%) | 5 (2.1%) | 13 (4.6%) | 4 (2.5%) | 0.3 |
Abbreviations: BCS, breast-conserving surgery; NAC, neoadjuvant chemotherapy; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; pCR, pathologic complete response; LR, local recurrence
Unknown in 178 patients
At median follow-up of 35 months (interquartile range [IQR] 24–48), 22 (3.2%) patients had developed an LR, with 5 occurring in pre-NAC BCSe patients, 13 in BCSi patients who downstaged and had BCS, and 4 in BCSi patients who downstaged and chose mastectomy. None of the 4 patients who developed LR after mastectomy received post-mastectomy RT. The Kaplan-Meier 4-year LR rate was 3.8% (95% confidence interval [CI] 2.1–5.5) overall and was similar between groups: 1.9% (95% CI 0.04–3.8) among pre-NAC BCSe, 6.3% (95% CI 2.6–10.0) among those who downstaged and had BCS, and 2.7% (95% CI 0.09–5.4) among those who downstaged and chose mastectomy (P = 0.17, Fig. 2). The crude median time to LR was 14 months (IQR 10–20) and the majority (n = 18, 82%) were isolated breast or chest wall recurrences, while 4 (18%) had synchronous breast or chest wall and regional nodal recurrences. Time to LR and location of LR were similar between groups (P = 0.3 and P = 0.2, respectively). Distant disease developed in 55 (8.0%) patients (7.4% vs. 7.4% vs. 10%, P = 0.6) and at last follow-up, 617 (90%) patients were alive with no evidence of disease (92% vs. 90% vs. 88%, P = 0.5).
Figure 2.
Local recurrence-free survival. (a) Overall and (b) stratified by BCS eligibility and type of surgery.
Abbreviations: LR, local recurrence; BCS, breast-conserving surgery.
Associations with development of LR were examined using Cox regression models and are summarized in Table 2. On univariate analysis, breast pCR (hazard ratio [HR] 0.20, 95% CI 0.05–0.87, P = 0.032) and LVI (HR 3.95, 95% CI 1.55–10.0, P = 0.004) were associated with development of LR, while clinical T stage and BCS eligibility pre-NAC were not (P > 0.5). On multivariable analysis, only LVI was independently associated with LR (HR 3.06, 95% CI 1.2–7.9, P = 0.02) (Table 2). Multiple imputation analysis to account for missing data did not affect this result; LVI remained the only covariate associated with LR (HR 3.24, 95% CI 1.33–7.86, P = 0.01).
TABLE 2.
Univariate and Multivariable Regression Analysis of Risk Factors for Development of Local Recurrence
| Univariate analysis | Multivariable analysis | |||||
|---|---|---|---|---|---|---|
| HR | 95% CI | P | HR | 95% CI | P | |
| Eligibility/surgery group | ||||||
| Initially BCSe and had BCS | Ref | – | – | Ref | – | – |
| Downstaged and had BCS | 2.43 | 0.9-6.8 | 0.09 | 2.70 | 0.8-9.4 | 0.1 |
| Downstaged and chose mastectomy | 1.28 | 0.3-4.8 | 0.7 | 0.78 | 0.2-3.9 | 0.8 |
| Age, years | 1.00 | 0.96-1.0 | > 0.9 | |||
| Clinical T stage | ||||||
| 1 | Ref | – | – | Ref | – | – |
| 2 | 0.87 | 0.2-3.1 | 0.8 | 0.90 | 0.2-4.4 | 0.9 |
| 3 | 2.72 | 0.7-10.3 | 0.14 | 2.06 | 0.4-11.6 | 0.4 |
| Clinical N stage | ||||||
| 0 | Ref | – | – | |||
| 1 | 1.04 | 0.5-2.4 | > 0.9 | |||
| 2* | NA | NA | > 0.9 | |||
| 3* | NA | NA | > 0.9 | |||
| Receptor status | ||||||
| ER+/HER2− | Ref | – | – | |||
| ER+/HER2+ | 0.30 | 0.06-1.4 | 0.13 | |||
| ER−/HER2+ | 1.18 | 0.3-4.0 | 0.8 | |||
| ER−/HER2− | 1.14 | 0.4-3.1 | 0.8 | |||
| Differentiation** | ||||||
| Moderate | Ref | – | – | |||
| Poor | 1.12 | 0.4–3.0 | 0.8 | |||
| Lymphovascular invasion | ||||||
| Absent | Ref | – | – | Ref | – | – |
| Present | 3.95 | 1.6-10.0 | 0.004 | 3.06 | 1.2–7.9 | 0.02 |
| Breast pCR (ypT0) | ||||||
| No | Ref | – | – | Ref | – | – |
| Yes | 0.20 | 0.05-0.8 | 0.03 | 0.18 | 0.02–1.4 | 0.10 |
Abbreviations: HR, hazard ratio; CI, confidence interval; BCSe, breast-conserving surgery-eligible; BCS, breast-conserving surgery; NA, not applicable; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; pCR, pathologic complete response
Too few patients with cN2 and cN3 tumors (n = 46) to report hazard ratio
Too few patients with well-differentiated tumors (n = 6) to report hazard ratio
DISCUSSION
This study in a large, consecutive cohort of patients with T1-3 breast cancer treated with modern NAC provides evidence that rates of LR after NAC and BCS are low, even among patients who were initially BCSi and downstaged with NAC.
As NAC is increasingly being used to downstage large primary tumors to BCS, evidence supporting the oncologic safety of this approach is of paramount importance. While early trials demonstrated no difference in survival or LR with the use of NAC versus postoperative chemotherapy2,3, the recent EBCTCG meta-analysis of 10 randomized trials including 4,756 patients treated between 1983 and 2002 raised concerns regarding the safety of this approach. This analysis revealed a statistically significant higher rate of LR among patients treated with NAC compared to upfront surgery followed by adjuvant therapy at a median follow-up of 9 years.4 While the included trials were carried out in the pre-trastuzumab era, did not report details on RT, and likely employed dated pathologic and localization techniques, the authors hypothesized that the increase in LR may be attributable to those who converted from initially BCSi to BCSe after NAC and underwent BCS.
LR rates among patients who downstage to BCSe have been examined in small subgroup analyses of two early randomized trials. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 trial of 1,523 women randomized to NAC versus adjuvant chemotherapy, the 9-year rate of LR was 15.9% among those who downstaged to BCS (n = 69), compared to 9.9% among those who were BCSe before NAC and had BCS (n = 434). This was not statistically significant after adjusting for age and tumor size (P = 0.14).6 The European Organisation for Research and Treatment of Cancer (EORTC) 10902 trial also reported comparable 10-year rates of LR among those who underwent BCS followed by adjuvant chemotherapy (n = 64, ref), those who were initially BCSe and had NAC followed by BCS (n = 63, HR 1.0, 95% CI 0.46–2.15), and those who downstaged with NAC to BCS (n = 58, HR 1.1, 95% CI 0.5–2.39, P = 0.97), respectively.7 These findings are consistent with the results of our study, with a 4-year LR rate of 1.9% observed among initially BCSe patients who had NAC, 6.3% among BCSi who downstaged and had BCS, and 2.7% among BCSi who downstaged but chose mastectomy (P = 0.2). Furthermore, our observed LR rates post-NAC are comparable with the 10-year cumulative incidences of LR of up to 9% reported in the NSABP trials after upfront BCS followed by RT and adjuvant chemotherapy among both node-positive and node-negative breast cancers.8,9 To our knowledge, this is the first contemporary study to evaluate local control in a cohort with prospectively determined BCS eligibility, including over 400 patients who successfully downstaged from BSCi to BCSe. While longer follow-up of our cohort will establish long-term LR rates, the absence of any significant association between BCS eligibility pre- and post-NAC with LR on univariate and multivariable analyses suggests that eligibility status at presentation by itself is not a predictor of local failure.
Recent studies have demonstrated that poor response to NAC is predictive of LR. In a single-institution analysis of 751 patients treated with modern NAC and BCS from 2005 to 2012, failure to achieve pCR was independently associated with LR (HR 8.9, 95% CI 2.1–37, P = 0.003), with a 5-year LR-free survival rate of 98.6% among those who experienced a pCR compared to 89.9% among those who did not (P = 0.007).10 Similarly, lack of breast pCR was predictive of LR (HR 1.4, 95% CI 1.1–1.8, P = 0.02) in a patient-level meta-analysis including 4,125 patients from 9 studies of BCT after NAC.11 In our current study, breast pCR was associated with LR on univariate analysis, but this did not reach statistical significance on multivariable analysis. This may be due to the low LR event rate in our study, as well as our short median follow-up; with longer follow-up associations with breast pCR may become evident. Notably, LVI, a known risk factor for recurrence12, was strongly associated with LR on univariate and multivariable analysis, highlighting this clinicopathologic feature as a primary driver of local failure. The observation that choosing a mastectomy did not lower rates of LR among patients who downstaged from BCSi to BCSe further underscores the impact of tumor biology, and not extent of local surgery, on local control.
The findings in this study support the safety of BCS after NAC among initially BCSi patients who downstage to BCSe. The perception that all breast tissue initially involved by tumor must be excised at time of surgery may lead to unnecessary mastectomies in this setting.13,14 While guidelines such as those published by the St. Gallen International Expert Consensus advise that resection of the entire tumor bed after neoadjuvant treatment is not necessary,15 practice remains highly variable. In a recent survey of all multidisciplinary teams from breast units in the United Kingdom, 26% of centers reported resection of the original tumor footprint regardless of clinical and radiologic response.13 Similarly, in the NeoALLTO trial of neoadjuvant treatment among HER2+ cancers, despite dramatic improvements in pCR rates with dual HER2 blockade, BCS rates did not increase, and use of BCS remained most frequent among those who were deemed BCSe at diagnosis.16 However, past data have demonstrated the safety of limiting resection to residual viable tumor, including a retrospective study of 509 consecutive patients with T1-3N0-2 cancers treated in prospective trials of chemotherapy from 1998 to 2005. That study found that after NAC, there was a significant reduction in lumpectomy volume among tumors sized > 2 cm at presentation, and no difference in re-excision rate or LR at 33 months, when compared to those who received postoperative chemotherapy.17 Appropriate margin width after NAC also remains controversial, but multiple studies have demonstrated that no tumor on ink, similar to the primary surgery setting, is associated with excellent local control after NAC and BCS.18-21 While long-term outcomes data are forthcoming, contemporary data including results from our current study emphasize the opportunity for optimizing surgical therapy and decreasing the burden of overtreatment.
Limitations of our study include its retrospective, single-institution nature and relatively short median follow-up of 35 months. However, we have examined a large, consecutive cohort of patients treated with modern NAC, with prospective determination of BCS eligibility by the treating surgeon and standardized medical, surgical, and pathologic techniques. Additionally, though most recurrences among HER2+ and triple-negative patients, who comprise over 70% of our study population, occur within 5 years,22-24 further follow-up will be valuable to establish long-term LR rates after treatment with NAC and BCS.
In conclusion, in this contemporary population of operable breast cancers treated with NAC, the 4-year rate of LR was similar among initially BCSi patients who downstaged to BCSe and had BCS, and those who were BCSe throughout and had BCS. Choosing to undergo mastectomy did not improve LR rates among those who downstaged. These results support the safety of avoiding mastectomy in initially ineligible patients who downstage with modern NAC. For many patients, this approach affords an opportunity for surgical de-escalation to minimize the burden of treatment without compromising oncologic outcomes.
FUNDING SUPPORT
The preparation of this study was supported in part by NIH/NCI Cancer Center Support Grant No. P30 CA008748 to Memorial Sloan Kettering Cancer Center.
Footnotes
CONFLICT OF INTEREST DISCLOSURES
This study was presented in virtual poster format at the Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care, March 18-19, 2021. Dr. Monica Morrow has received honoraria from Exact Sciences and Roche. All other authors have no conflict of interests or commercial interests to disclose. All authors have read and approved the manuscript. This manuscript is not under consideration elsewhere.
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