On 13 March 2020, the American College of Surgeons (ACS) issued a guideline that requested that all hospitals delay elective surgeries to conserve resources for patients infected with SARS CoV-2 virus.1 The objective of this study was to examine short-term pathologic outcomes of patients with breast cancer who experienced delays during this time period.
Patients and Methods
This was a retrospective single-institution chart review of patients who were scheduled for a surgical procedure between 16 March and 30 April 2020, but then were delayed because of the ACS guideline statement. Patients assigned to neoadjuvant therapy during this time period were excluded. Surgical delay was defined as date of diagnosis to date of surgery scheduled. We compared clinical and pathologic tumor characteristics for invasive and noninvasive cancers by comparing the largest size that was found on ultrasound, mammogram, or MRI and using methodology from our previous publication.2
Results
There was a total of 83 patients, of whom 57 (68.7%) had invasive cancer and 26 (31.3%) had ductal carcinoma in situ (DCIS). The median delay for all patients was 94 ± 49 days. Of 54 patients with hormone receptor positive (HR+) and Her2neu-negative disease, 46 (80.7%) received neoadjuvant endocrine therapy (NET) prior to surgery (Table 1). None of our patients with DCIS received NET. There were no significant differences in clinical and pathologic tumor size or grade for invasive or DCIS lesions (Table 2). Over 70% of patients for both invasive and DCIS lesions had the same clinical and pathologic tumor grade. Over 80% of patients with invasive disease had a final pathologic tumor size that was concordant with the clinical tumor size at presentation, and only three (5.5%) had a final pathologic tumor size that was greater than the clinical tumor size at presentation. Only 14 (60.9%) of DCIS lesions had a final pathologic tumor size that was concordant with the clinical tumor size at presentation, and 3 (13.0%) had a final pathologic tumor size that was greater than the clinical tumor size at presentation. Nine (34.6%) of DCIS lesions were upstaged to invasive cancer at surgical resection; all were American Joint Committee on Cancer (AJCC) T1N0 cancers.
Table 1.
Patient and tumor characteristics (n = 112) prior to surgical resection
| Invasive cancer (n = 57) | DCIS (n = 26) | |
|---|---|---|
| Age, years | 68 ± 12 | 64 ± 12 |
| Race | ||
| White | 37 (64.9%) | 15 (57.7%) |
| Black | 3 (5.3%) | 2 (7.7%) |
| Hispanic | 2 (3.5%) | 0 (0%) |
| API | 1 (1.8%) | 4 (15.4%) |
| Other | 14 (24.6%) | 5 (19.2%) |
| Mean delay in surgery in days | 85 ± 45 | 83 ± 33 |
| Clinical tumor stage (anatomic) | T1N0 35 (61.4%) | TisN0 15 (100%) |
| T1N1 4 (7.0%) | ||
| T2N0 3 (5.3%) | ||
| T2N1 6 (10.5%) | ||
| T2N3 1 (1.8%) | ||
| T3N0 1 (1.8%) | ||
| T3N1 1 (1.8%) | ||
| T3N2 1 (1.8%) | ||
| T3N3 1 (1.8%) | ||
| T4NX 1 (1.8%) | ||
| Receptor status | ||
| HR+HER2neu− | 52 (91.2%) | NA |
| HR+ HER2neu+ | 1 (1.8%) | NA |
| HR−HER2neu+ | 0 (0%) | NA |
| HR−HER2neu− | 2 (3.5%) | NA |
| HR+ HER2neu not assessed | 2 (3.5%) | 16 (80%) |
| HR− HER2neu not assessed | 0 (0%) | 4 (20%) |
| Neoadjuvant therapy | ||
| Hormonal therapy | 46 patients (out of 54 HR+ patients, 80.7%) | 4 (15.4%) |
| Chemotherapy | 2 patients (3.5%)* | 0 (0%) |
| High risk lesion pathology | NA | NA |
*Patients had received neoadjuvant therapy several months prior to March 2020
API Asian/Pacific Islander, HR Hormone receptor, DCIS Ductal carcinoma in situ
Table 2.
Pathologic outcomes at surgical resection
| Invasive disease (n = 57) | DCIS (n = 26) | |
|---|---|---|
| Tumor size | ||
| Clinical size | 2.1 ± 2.1 | 1.6 ± 1.3 |
| Pathologic size | 1.9 ± 1.9 | 1.4 ± 1.2 |
| Size the same on final pathology | 46 (83.6%) | 14 (60.9%) |
| Size smaller on final pathology | 6 (10.9%) | 6 (26.1%) |
| Size larger on final pathology | 3 (5.5%) | 3 (13.0%) |
| Tumor grade* | ||
| Grade stayed the same | 40 (70.1%) | 19 (73.0%) |
| Grade I to II or III | 2 (3.5%) | 0 (0%) |
| Grade II to III | 0 (0%) | 0 (0%) |
| Grade II to I | 9 (15.8%) | 1 (3.8%) |
| Grade III to II or I | 2 (3.5%) | 3 (11.5%) |
| Nodal status | ||
| Final node status same as clinical node status | 30 (73%) | 6 (100%) |
| Clinical node status N1, pathologic N0 | 0 (0%) | 0 (0%) |
| Clinical node status N0, pathologic N1 | 11 (26.8%) | 0 (0%) |
| Tumor upgrade | ||
| DCIS | NA | NA |
| Invasive disease | NA | 9 (34.6%) (all T1N0) |
*Clinical tumor size on imaging compared to pathologic tumor size
DCIS Ductal carcinoma in situ
Discussion
Time from diagnosis to first surgery at our institution ranges from 30 to 35 days, but during the time of this study it was approximately 85 days. Nonetheless, our findings show little impact for short-term outcomes of tumor size or grade. Nodal status was within expected numbers given the fact that clinical examination of the axillary nodes can miss nodal metastases. Historically, it has been known that there are differences between tumor size on imaging and final pathology. Our previous study showed that there was concordance between imaging tumor size and pathologic size approximately 49–55% of the time.2 In this study, we show concordance rates of 80% between imaging and pathologic tumor size, and the imaging tumor size was larger than pathologic size only 5% of the time. The lack of tumor progression for tumor size and tumor grade for patients with invasive disease can likely be attributed to the fact that 80% of patients with HR+ disease were placed on NET. Older randomized trials have shown no survival difference between those elderly patients on hormonal therapy who underwent surgery versus those that did not undergo surgery, but progression-free survival was worse in those who did not have surgery.3 However, progression of disease was not observed right away; in one trial the median time interval to progression of disease was 1.69 years.3 Clinical trials examining NET have shown low rates of tumor progression. In one study, only 8% of patients on tamoxifen and 1% on an aromatase inhibitor at 168 days (24 weeks) experienced progression of disease.4 One retrospective study showed that 1 year of treatment with letrozole resulted in significant regression and < 10% of progression of disease.5 This study demonstrates the safety and efficacy of a NET approach to patients with HR+ disease whose surgeries were delayed.
On the other hand, our patients with DCIS had higher tumor upstage rates than those reported in literature, and approximately 60% were concordant on imaging, although this size discrepancy is more common with DCIS than invasive cancers.6 We did not routinely place patients with DCIS on NET, though the guidelines at the time stated that hormonal therapy for DCIS cases could “be considered.”7 A retrospective study showed that 14% of patients with DCIS with a delay of 91–120 days were upstaged to invasive cancer.6 Our median delay was 83 days, but approximately a third of the patients were upstaged to invasive cancer. Future studies are needed to further evaluate disease progression during the pandemic.
Our numbers are small, and larger, multi-institutional studies are needed to validate our findings. However, these findings can provide some reassuring data that surgical delays for patients with HR+ disease did not result in significantly larger tumors.
Disclosures
None.
Footnotes
Publisher's Note
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References
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