Should breast surgery be considered for patients with de novo metastatic inflammatory breast cancer?

INTRODUCTION: We aimed to identify factors predicting surgery for de novo stage IV inflammatory breast cancer (IBC) and determine the association of surgery with overall survival (OS). METHODS: Female patients with unilateral AJCC clinical stage IV IBC treated 2010-2018 in the NCDB were identified. Logistic regression and multivariable proportional Cox hazards regressions determined factors associated with treatment and OS. RESULTS: Of 1049 patients, 29.1% underwent breast surgery (BS) and 70.9% had no surgery (NS). Increasing age and more recent treatment year were significantly associated with NS. 2-Year OS was superior in BS patients (71% vs 38% NS). Single-site and bone-only metastasis had no association with treatment type or OS. CONCLUSION: Contrary to guidelines, 1/3 of de novo stage IV IBC patients underwent BS, and had an independent OS benefit irrespective of extent or site of metastasis. Further research is needed to determine which patients with stage IV IBC should undergo BS.

Using MammaPrint on core needle biopsy to guide the need for axillary staging during breast surgery.

BACKGROUND: At present, the only opportunity to omit axillary staging is with Choosing Wisely criteria for women ages >70 y with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. However, many women are diagnosed when pathologic node status-negative, raising the question of additional opportunities to omit sentinel lymph node biopsy. We sought to investigate the association between MammaPrint, a genomic test that estimates estrogen receptor-positive breast cancer recurrence risk, and pathologic node status, with the aim that low-risk MammaPrint could be considered for omission of sentinel lymph node biopsy if associated with pathologic node status-negative. METHODS: A single-institution database was queried for all women with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer with breast surgery as their first treatment and MammaPrint performed from 2020 to 2021. Patient and tumor factors, including MammaPrint score, were compared with axillary node status for correlation. RESULTS: A total of 668 women met inclusion criteria, with a median age of 66 y. MammaPrint was low-risk luminal A in 481 (72%) and high-risk luminal B in 187 (28%). At the time of breast surgery, 588 (88%) had sentinel lymph node biopsy, 27 (4%) had axillary lymph node dissection, and 53 (7.9%) had no axillary staging. Most women in both the pathologic node status-negative and pathologic node status-positive cohorts had low-risk MammaPrint (355 [73.3%] pathologic node status-negative vs 91 [69.5%] pathologic node status-positive), and women with low-risk MammaPrint did not have a significantly lower risk of pathologic node status-positive (P = .377). CONCLUSION: Low-risk MammaPrint does not predict lower risk of pathologic node status-positive breast cancer. Based on our results, genomic testing does not appear to provide additional personalization for the ability to omit sentinel lymph node biopsy for patients outside of the Choosing Wisely guidelines.

Validation of the PREDICT Prognostication Tool in US Patients With Breast Cancer.

BACKGROUND: PREDICT is an online prognostication tool derived from breast cancer registry information on approximately 6,000 women treated in the United Kingdom that estimates the postsurgical treatment benefit of surgery alone, chemotherapy, trastuzumab, endocrine therapy, and/or adjuvant bisphosphonates in early-stage breast cancer. Our aim was to validate the PREDICT algorithm in predicting 5- and 10-year overall survival (OS) probabilities using real-world outcomes among US patients with breast cancer. METHODS: A retrospective study was performed including women diagnosed with unilateral breast cancer in 2004 through 2012. Women with primary unilateral invasive breast cancer were included. Patients with bilateral or metastatic breast cancer, no breast surgery, or missing critical clinical information were excluded. Prognostic scores from PREDICT were calculated and external validity was approached by assessing statistical discrimination through area under time-dependent receiver-operator curves (AUC) and comparing the predicted survival to the observed OS in relevant subgroups. RESULTS: We included 708,652 women, with a median age of 58 years. Most patients were White (85.4%), non-Hispanic (88.4%), and diagnosed with estrogen receptor-positive breast cancer (79.6%). Approximately 50% of patients received adjuvant chemotherapy, 67% received adjuvant endocrine therapy, 60% underwent a partial mastectomy, and 59% had 1 to 5 axillary sentinel nodes removed. Median follow-up time was 97.7 months. The population's 5- and 10-year OS were 89.7% and 78.7%, respectively. Estimated 5- and 10-year median survival with PREDICT were 88.3% and 73.8%, and an AUC of 0.77 and 0.76, respectively. PREDICT performed most poorly in patients with high Charlson-Deyo comorbidity scores (2-3), where PREDICT overestimated OS. Sensitivity analysis by year of diagnosis and HER2 status showed similar results. CONCLUSIONS: In this prognostic study utilizing the National Cancer Database, the PREDICT tool accurately predicted 5- and 10-year OS in a contemporary and diverse population of US patients with nonmetastatic breast cancer.

Presurgical Oral Tamoxifen vs Transdermal 4-Hydroxytamoxifen in Women With Ductal Carcinoma In Situ: A Randomized Clinical Trial.

Importance: Oral tamoxifen citrate benefits women with ductal carcinoma in situ (DCIS), but concern about toxic effects has limited acceptance. Previous pilot studies have suggested transdermal 4-hydroxytamoxifen gel has equivalent antiproliferative efficacy to oral tamoxifen, with low systemic exposure. Objective: To demonstrate that 4-hydroxytamoxifen gel applied to the breast skin is noninferior to oral tamoxifen in its antiproliferative effect in DCIS lesions. Design, Setting, and Participants: This randomized, double-blind, phase 2 preoperative window trial was performed at multicenter breast surgery referral practices from May 31, 2017, to January 27, 2021. Among 408 women with estrogen receptor-positive DCIS who were approached, 120 consented and 100 initiated study treatment. The most common reasons for nonparticipation were surgical delay, disinterest in research, and concerns about toxic effects. Data were analyzed from January 26, 2021, to October 5, 2022. Intervention: Random assignment to oral tamoxifen citrate, 20 mg/d, and gel placebo or 4-hydroxytamoxifen gel, 2 mg/d per breast, and oral placebo, for 4 to 10 weeks, followed by DCIS resection. Main Outcomes and Measures: The primary end point was absolute change in DCIS Ki-67 labeling index (Ki67-LI). Secondary end points included 12-gene DCIS Score, breast tissue tamoxifen metabolite concentrations, tamoxifen-responsive plasma protein levels, and patient-reported symptoms. Noninferiority of Ki67-LI reduction by 4-hydroxytamoxifen gel was tested using analysis of covariance; within- and between-arm comparisons were performed with paired t tests for mean values or the Wilcoxon rank sum test for medians. Results: Of 90 participants completing treatment (mean [SD] age, 55 [11] years; 8 [8.9%] Asian, 16 [17.8%] Black, 8 [8.9%] Latina, and 53 [58.9%] White), 15 lacked residual DCIS in the surgical sample, leaving 75 evaluable for the primary end point analysis (40 in the oral tamoxifen group and 35 in the 4-hydroxytamoxifen gel group). Posttreatment Ki67-LI was 3.3% higher (80% CI, 2.1%-4.6%) in the 4-hydroxytamoxifen gel group compared with the oral tamoxifen group, exceeding the noninferiority margin (2.6%). The DCIS Score decreased more with oral tamoxifen treatment (-16 [95% CI, -22 to -9.4]) than with 4-hydroxytamoxifen gel (-1.8 [95% CI, -5.8 to 2.3]). The median 4-hydroxytamoxifen concentrations deep in the breast were nonsignificantly higher in the oral tamoxifen group (5.7 [IQR, 4.0-7.9] vs 3.8 [IQR, 1.3-7.9] ng/g), whereas endoxifen was abundant in the oral tamoxifen group and minimal in the 4-hydroxytamoxifen gel group (median, 13.0 [IQR, 8.9-20.6] vs 0.3 [IQR, 0-0.3] ng/g; P < .001). Oral tamoxifen caused expected adverse changes in plasma protein levels and vasomotor symptoms, with minimal changes in the transdermal group. Conclusions and Relevance: In this randomized clinical trial, antiproliferative noninferiority of 4-hydroxytamoxifen gel to oral tamoxifen was not confirmed, potentially owing to endoxifen exposure differences. New transdermal approaches must deliver higher drug quantities and/or include the most potent metabolites. Trial Registration: ClinicalTrials.gov Identifier: NCT02993159.

Estimating the overall survival benefit of adjuvant chemo-endocrine therapy in women over age 50 with pT1-2N0 early stage breast cancer and 21-gene recurrence score ≥26: A National Cancer Database analysis.

BACKGROUND: Validation studies of the 21-gene recurrence score (RS) previously demonstrated that adjuvant chemotherapy plus endocrine therapy (CET) was associated with a significant survival benefit in women with node negative breast cancer (BC) and RS >31. However, the TAILORx trial, did not quantify the benefit of adjuvant CET in older women with node negative hormone receptor positive (HR+) BC with RS ≥26. We hypothesized that CET would be associated with improved overall survival (OS) compared to endocrine therapy (ET) in women >50 with HR+/HER2-node negative BC and RS ≥26. METHODS: The National Cancer Database (NCDB) was queried to identify women >50 with RS ≥26 ER+/HER2-BC pT1-2N0M0. Chi-square and logistic regression analysis determined the difference between ET and CET. OS was analyzed using a multivariable Cox model. RESULTS: We included 16,745 women-4740 (28.3%) received ET and 12,005 (71.7%) received CET. Women who received CET had: moderately (OR = 1.853, p < 0.001) or poorly/undifferentiated tumors (OR = 3.875, p < 0.001), pT2 (OR = 1.356, p < 0.001), or lymph-vascular invasion (OR = 1.206, p = 0.001). After accounting for demographic and oncologic factors, 5-year OS rates were significantly superior in women receiving CET vs. ET alone (95.4% vs. 92.0%, Hazard Ratio = 0.680, p < 0.001). CONCLUSIONS: We observed that CET was associated with a clinically and statistically significant higher OS compared to ET alone in women >50 years of age with RS ≥26 pT1 and pT2 N0M0 HR+/HER2-breast cancer, and which suggests that cytotoxic chemotherapy has an impact on reducing mortality that is independent of induction of premature ovarian failure.

Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in ER+/HER2- breast cancer pts with 1-3 positive nodes and oncotype DX recurrence score 20 to 25: an NCDB analysis.

Background: The RxPONDER trial found that among breast cancer patients with estrogen receptor positive (ER+) breast cancer, 1-3 positive axillary nodes, and a recurrence score of ≤25, only pre-menopausal women benefitted from adjuvant chemoendocrine therapy; postmenopausal women with similar characteristic did not benefit from adjuvant chemotherapy. We aimed to replicate the RxPonder trial using a larger patient cohort with real world data to determine whether a RS threshold existed where adjuvant chemotherapy was beneficial regardless of age. Methods: The National Cancer Database (NCDB) was queried for women with ER+, human epidermal growth factor receptor 2 (HER2) negative breast cancer, 1-3 positive axillary nodes, and RS ≤25 who received endocrine (ET) only or chemo-endocrine therapy (CET). Cox regression interaction was explored between CET and age as a surrogate for menopausal status. Results: The final analytic cohort included 28,427 eligible women: 7,487 (26.3%) received adjuvant CET and 20,940 (73.7%) ET. In the entire cohort, RS had a normal distribution, with a median score of 14. After correcting for demographic and clinical variables, a threshold effect was observed with RS >20 being associated with a significantly inferior overall survival (OS) (P value range: < 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age <=50: HR = 0.334, P=0.002; age>50: HR=0.521, P=0.019). Conclusion: Among women with ER+/HER2- breast cancer with 1-3 positive nodes, and a RS of 20-25-in contrast to the RxPONDER trial-we observed that CET was associated with an OS benefit in women regardless of age.

MYO10 regulates genome stability and cancer inflammation through mediating mitosis.

Genomic instability can promote inflammation and tumor development. Previous research revealed an unexpected layer of regulation of genomic instability by a cytoplasmic protein MYO10; however, the underlying mechanism remained unclear. Here, we report a protein stability-mediated mitotic regulation of MYO10 in controlling genome stability. We characterized a degron motif and phosphorylation residues in the degron that mediate ß-TrCP1-dependent MYO10 degradation. The level of phosphorylated MYO10 protein transiently increases during mitosis, which is accompanied by a spatiotemporal cellular localization change first accumulating at the centrosome then at the midbody. Depletion of MYO10 or expression of MYO10 degron mutants, including those found in cancer patients, disrupts mitosis, increases genomic instability and inflammation, and promotes tumor growth; however, they also increase the sensitivity of cancer cells to Taxol. Our studies demonstrate a critical role of MYO10 in mitosis progression, through which it regulates genome stability, cancer growth, and cellular response to mitotic toxins.

Adjuvant Therapy in Breast Cancer Patients With Microscopic Residual Disease.

INTRODUCTION: Surgical resection is the gold standard for early-stage breast cancer. Positive surgical margins are associated with poor outcome. Endocrine therapy (ET) is recommended as primary systemic treatment for hormone receptor positive (HR+) breast cancer after surgery. We hypothesized that chemoenocrine therapy (CET) would not be associated with improved survival relative to ET for patients with positive margins. MATERIALS AND METHODS: The National Cancer Database was queried for pathologic stage I HR + HER2-breast cancer patients treated with partial mastectomy and adjuvant whole-breast irradiation between 2004 and 2017. The adjuvant treatment approaches to positive surgical margins were investigated and compared. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression. RESULTS: Among 228,453 patients, a positive surgical margin (microscopic residual disease, R1) was identified in 3561 (1.6%) patients. Compared with complete resections, positive margin was associated with inferior overall survival (hazard ratio [HR] = 1.276, P = 0.003). Among the R1 patients, 78.7% received ET only, 11.7% received CET, 1.2% received chemotherapy only, and 8.5% received no systemic therapy. After controlling for patient, facility, and tumor characteristics, ET provided greatest survival benefit (relative to no therapy, HR = 0.378, P < 0.001) followed by CET (HR = 0.446, P = 0.020). Compared with ET alone, CET is not associated with additional overall survival benefit (HR = 1.179, P = 0.595). CONCLUSIONS: CET appeared not to be associated with an improved overall survival in early stage HR + HER2-breast cancer with microscopic residual disease relative to ET. Positive surgical margins therefore are probably not a relevant clinical factor for adjuvant chemotherapy decision-making.

Breast MRI assists in decision-making for surgical excision of atypical ductal hyperplasia.

BACKGROUND: Atypical ductal hyperplasia diagnosed on percutaneous breast biopsy typically undergoes surgical excision, upgrading to invasive breast cancer or ductal carcinoma in situ in 10% to 53%. In efforts to limit excision to those with highest upgrade risk, we sought to determine if breast magnetic resonance imaging has value in predicting upgrade. In this study, we will describe magnetic resonance imaging presentation of atypical ductal hyperplasia and assess magnetic resonance imaging accuracy in predicting upgrade. METHODS: All female patients ≥18 years with atypical ductal hyperplasia on percutaneous breast biopsy undergoing magnetic resonance imaging from 2008 to 2020 were included. Patient demographics, imaging presentation, magnetic resonance imaging enhancement kinetic curves, and pathology features were captured. Categorical variables were analyzed using Fisher exact to test for association between variables and upgrade. Continuous variables were analyzed using t tests. RESULTS: Magnetic resonance imaging was performed for 125 percutaneous breast biopsy with atypical ductal hyperplasia: 67 after and 58 before atypical ductal hyperplasia diagnosis. On magnetic resonance imaging, atypical ductal hyperplasia site had no enhancement in 45 (36%), nonmass enhancement in 50 (40%), and mass enhancement in 30 (24%). In total, 28% had atypical ductal hyperplasia diagnosed by magnetic resonance imaging-guided percutaneous breast biopsy. Surgical excision was performed for 96 (76.8%) and 15 (15.6%) upgraded (11 ductal carcinoma in situ, 4 invasive breast cancer). All 15 upgrades had enhancement. Any kinetic pattern enhancement was significantly associated with upgrade (P = .009) with upgrade most strongly associated with type III washout. The lowest risk for upgrade was pure atypical ductal hyperplasia and no magnetic resonance imaging enhancement (0%, n = 25). CONCLUSIONS: Active monitoring may be safely offered to women with pure atypical ductal hyperplasia on percutaneous breast biopsy when magnetic resonance imaging shows no enhancement. Any enhancement at atypical ductal hyperplasia site, particularly type III washout kinetics, should continue to undergo excision.

Safety of de-escalation of surgical intervention for atypical ductal hyperplasia on percutaneous biopsy: One size does not fit all.

BACKGROUND: Oncologic safety of active monitoring (AM) for atypical ductal hyperplasia (ADH) on core-needle biopsy (CNB) is not well defined. We sought to define oncologic outcomes for AM to manage ADH meeting institutional predefined low-risk criteria (LOW). METHODS: ADH was diagnosed on CNB from 10/2015-03/2020. LOW (pure ADH, size <1 cm, >50% removed by CNB, <3 foci, and no necrosis) patients were offered AM; all others were recommended for surgical excision. Oncologic outcomes were compared for AM and surgery. RESULTS: 111 were included, 21 (19%) meeting LOW. AM occurred in 18 (86%) while 3 elected for excision (with 0% upgrade). Of the 18 LOW in AM, 2 required additional CNB (none at ADH site): 0% were diagnosed with cancer over median 23 month follow-up. CONCLUSIONS: There were no missed cancers at ADH site during AM for LOW, confirming the oncologic safety of AM in this select group.

Guideline-Consistent Treatment for Inflammatory Breast Cancer Provides Associated Survival Benefit Independent of Age.

BACKGROUND: Guideline-consistent treatment (GCT) for inflammatory breast cancer (IBC) includes neoadjuvant chemotherapy (NAC), modified radical mastectomy (MRM), and radiation. We hypothesized that younger patients more frequently receive GCT, resulting in survival differences. METHODS: Using the National Cancer Database (2004-2018), female patients with unilateral IBC (by histology code and clinical stage T4d) were stratified by age (< 50, 50-65, > 65 years). Factors associated with NAC, MRM, radiation, and "GCT" (defined as all three treatments) were identified using multivariable logistic regression. Multivariable Cox proportional hazards regression identified predictors of overall survival. RESULTS: Of 3278 IBC patients, 30% were younger than 50 years, 44% were 50-65 years of age, and 26% were older than 65 years. The youngest group comprised the greatest proportion of non-White patients ([35%] vs. [29%] age 50-65 years and [23%] age > 65 years, p < 0.001) and was most often treated at academic facilities ([33%] vs. [28%] age 50-65 years; and [23%] age > 65, p < 0.001). Patients older than 65 years received NAC, MRM, and radiation less frequently, and only 35% underwent GCT (vs. [57%] age 50-65 years and [52%] age < 50 years; p < 0.001). On multivariable logistic regression, age older than 65 years independently predicted omission of NAC (odds ratio [OR], 0.36), MRM (OR, 0.56), and radiation (OR, 0.56) (all p < 0.001), and patients older than 65 years also were less likely to undergo GCT than patients 50-65 years of age (OR, 0.65; p = 0.001). GCT was associated with superior overall survival in all three age groups ([hazard ratio {HR}, 0.61] age < 50 years, [HR, 0.62] age 50-65 years, [HR, 0.53] age > 65 years; all p < 0.001). CONCLUSION: Advanced age alone should not limit receipt of GCT for IBC. Multimodal care should be performed for IBC patients of all ages to improve oncologic outcomes for this aggressive breast cancer subtype.

Rethinking Routine Surgical Excision for all Radial Sclerosing Lesions of the Breast.

INTRODUCTION: The need for routine surgical excision of a radial sclerosing lesions (RSL) of the breast identified on percutaneous biopsy remains controversial, as contemporary upgrade rates are lower than historically cited. MATERIALS AND METHODS: A prospectively-maintained database of high-risk breast biopsies undergoing multidisciplinary review at a single institution was queried to identify cases of RSL from 2/2015 to 11/2020. Demographic, radiologic, and pathologic variables were summarized using frequencies and analyzed in association with RSL excision status using mixed-effects logistic regression or Fisher's exact tests. RESULTS: 217 RSL were identified, diagnosed at a mean age of 57 y. The median imaging size was 1.3 cm and the majority had estimated >50% of the target removed by core needle biopsy. 32.3% underwent surgical excision of the RSL biopsy site and 2/70 (2.9%) upgraded to ductal carcinoma in situ (DCIS) on final surgical pathology. Upgrade was significantly higher for atypical RSL (P = 0.02). None of the RSL (n = 60) without atypia who had undergone excision were upgraded. For those omitting surgical excision, there was no subsequent breast cancer diagnosis at the RSL site over a mean follow-up of 23 mo. CONCLUSIONS: Surgical excision may be omitted for RSL without atypia as this group has 0% risk of upgrade after multidisciplinary review.

Age disparities in triple-negative breast cancer treatment and outcomes: An NCDB analysis.

BACKGROUND: Race, access to care, and molecular features result in outcome disparities in triple-negative breast cancer (TNBC). We sought to determine the role of age in TNBC disparity by hypothesizing that younger patients receive more comprehensive treatment, resulting in survival differences. METHODS: The National Cancer Database was used to identify women with unilateral TNBC treated from 2005 through 2017. Patients were stratified by age (≤40, 41-70, >70); demographics, clinical characteristics, and treatment factors were compared. Logistic regression determined factors associated with treatment received. Survival outcomes were analyzed using a stratified log-rank test. RESULTS: Of the 168,715 patients, 16,287 (9.6%) were ≤40 years. Patients ≤40 were significantly more likely to present at higher clinical stage (P < .001) and receive neoadjuvant chemotherapy (NAC, P < .001). Bilateral mastectomy was the most common surgery for patients ≤40 (37%), whereas partial mastectomy was most often used in patients 41 to 70 years old (48%) and those >70 (49%) (P < .001). Patients ≤40 years were significantly more likely to undergo both NAC and mastectomy than those >40 (odds ratio 1.5, both P < .05) despite a greater in-breast tumor response in the youngest patients. Patients treated with mastectomy and axillary lymph node dissection had inferior survival outcomes compared to those treated with partial mastectomy and sentinel lymph node biopsy across all 3 age groups (P < .001). CONCLUSION: The clinical characteristics of TNBC differ significantly at the extremes of age, likely driving treatment decisions. Although patients ≤40 present with a more advanced disease and appropriately receive NAC, they also undergo more extensive surgery that does not yield a survival benefit. Further research is needed to determine if age disparity is due to oncologic factors or patient and provider preferences.

Upgrade rates of intraductal papilloma with and without atypia diagnosed on core needle biopsy and clinicopathologic predictors.

Surgical excision of breast intraductal papilloma (IDP) without atypia diagnosed on core needle biopsy (CNB) is controversial as the risk of upgrade to malignant lesions is not well established. This study investigates upgrade rates of benign and atypical IDP to ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) and clinicopathologic predictors. We identified 556 cases of IDP diagnosed on CNB at a single institution from 2010 to 2020 after excluding patients with a history of breast carcinoma, ipsilateral high-risk lesion, radiologic/pathologic discordance, or less than 2 years of follow-up if no excision within 1 year. Of these, 97 biopsies were consistent with atypical IDP and 459 were benign IDP. Surgical excision was performed for 318 (57.2%), and the remaining 238 (42.8%) underwent active monitoring. The upgrade rate for IDP without atypia was 2/225 (0.9%; 1 DCIS and 1 IC). Of 93 surgically excised atypical IDPs, 19 (20.4%) upgraded (14 DCIS and 5 IC). Of 238 nonexcised IDPs followed clinically (range, 24-140 months, mean 60 months), there was no subsequent breast cancer diagnosed at the IDP site on follow-up. Mean age of patients was 56 yr ± 12.6 SD without upgrade, 63 yr ± 10.6 SD (P = .027) with DCIS, and 61 yr ± 10.8 SD (P = .35) with IC. Atypical IDP was more likely to upgrade if biopsied by stereotactic guidance (8/19, 42.1% P = .035). At our institution, we had an exceedingly low upgrade rate for benign IDP. Overall, patients with upgrade to DCIS were older. For atypical IDP, upgrade was seen in higher proportions of stereotactic biopsies.

A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis.

BACKGROUND: Small invasive breast cancers (BCs) with tumor sizes ≤5 mm (T1a) are associated with an excellent prognosis without systemic therapy. Although HER2 overexpression (HER2+) is associated with a higher risk of recurrence and poorer clinical outcomes, in the absence of HER2 directed therapy, it remains unclear whether adjuvant systemic therapy is necessary in node-negative patients diagnosed with HER2+ invasive BCs ≤5 mm (pT1aN0M0). METHODS: The National Cancer Database was searched to identify patients diagnosed with HER2+ pT1aN0M0 BCs from 2004 to 2017. The cohort was stratified by treatment status: local therapy alone or local plus adjuvant systemic therapy. A 1:1 propensity match was performed. Overall survival (OS) was analyzed using stratified multivariable Cox proportional hazards regression analyses. RESULTS: Of the 8948 patients found, 4026 (45.0%) underwent surgery alone, and 4922 (55.0%) received surgery plus systemic therapy. Patients with either moderately differentiated (odds ratio [OR], 2.053; P < .001) or poorly/undifferentiated tumors (OR, 3.780; P < .001) or with the presence of lymphovascular invasion (OR, 3.351; P < .001) were more likely to have received systemic therapy. Propensity matching generated 1162 pairs of patients who were hormone receptor positive (HR+) and 748 pairs who were hormone receptor negative (HR-). Propensity matching effectively reduced selection bias between study groups. In the matched cohort, the addition of systemic therapy was not associated with superior OS (hazard ratio for HR+, 1.613; P = .107, and hazard ratio for HR- 1.319; P = .369) compared with patients who received local therapy alone. CONCLUSIONS: In pT1aN0M0 HER2+ BC, the addition of adjuvant systemic therapy after surgical excision was not associated with improved OS compared with local therapy alone.

The clinical impact of MRI on surgical planning for patients with in-breast tumor recurrence.

OBJECTIVE: The objective of this study was to evaluate the clinical utility of breast MRI for patients with known in-breast tumor recurrence (IBTR). The aim was to determine if the addition of breast MRI altered surgical approach or multidisciplinary management. Previous studies have focused on using breast MRI for surgical planning for index breast cancers (BC) or detecting IBTR. However, the clinical impact of obtaining MRI in the setting of known IBTR has not been evaluated. METHODS: A single-institution retrospective chart review was performed to compare surgical approach and multidisciplinary management for patients diagnosed with isolated IBTR who did and did not undergo breast MRI following IBTR diagnosis. RESULTS: IBTR was identified in 69 patients, 46% of whom underwent MRI. There was no difference in the operative approach (p = 0.14) for IBTR patients who did and did not undergo breast MRI Additionally, there was no difference in multidisciplinary care, treatment order, metastatic disease identification, or mortality between cohorts. A relatively small subgroup of patients (n = 3) required change in surgical plan based on MRI results. Patients proceeding with surgery first who also underwent breast MRI experienced a significantly longer time to surgical intervention (p = 0.03). CONCLUSION: Breast MRI following IBTR diagnosis infrequently impacted clinical management, including surgical approach and multidisciplinary care. MRI for local disease assessment at the time of IBTR should be used selectively based on clinical concern.

Prognostic Significance of Lobular Carcinoma In-Situ (LCIS) Diagnosed Alongside Invasive Breast Cancer.

Purpose: Women with lobular carcinoma in-situ (LCIS) have an increased risk for developing breast cancer (BC) compared with the general population. However, little is known about the clinical implication of diagnosing LCIS concurrently with an invasive breast cancer. We aimed to define the rate of LCIS diagnosed concurrently with an invasive breast cancer and investigate the risk of contralateral breast cancer (CBC) during survivorship care. Materials and methods: A single center retrospective review over 6 years identified women with stage I-III BC who underwent lumpectomy or unilateral mastectomy. Patients with or without concurrent LCIS were compared using Chi-squared analyses to assess for differences in clinicopathologic factors and risk of future CBC (including invasive and in-situ disease). Results: Of 1808 patients, 16.6% (n = 301) had LCIS concurrent with their index breast cancer. Patients with LCIS had a higher rate of subsequent CBC development than those without LCIS (3.3% versus 1.0%, P = .004). The risk ratio for patients with LCIS developing subsequent CBC compared with those without LCIS was 3.3 (95% confidence interval [CI]: 1.5-7.3). Conclusions: Patients with LCIS diagnosed concurrently with their index breast cancer at surgery are at higher risk for subsequent CBC than those without LCIS. The evidence from this study suggest that it may be appropriate for women with LCIS diagnosed alongside an index breast cancer to consider on-going high-risk screening during survivorship care.