Lack of Either Estrogen or Progesterone Receptor Expression Is Associated with Poor Survival Outcome among Luminal A Breast Cancer Subtype

Background

This study was designed to evaluate the impact of lack of either estrogen receptor (ER) or progesterone receptor (PR) on characteristics and outcomes among luminal A breast cancer subtype treated with endocrine with or without chemotherapeutic agents.

Methods

The luminal A subtype was categorized into three subgroups: ER+/PR+, ER+/PR?, and ER?/PR+. All tumors were human epidermal growth factor receptor 2 (HER2) negative. Clinicopathological features and survival were analyzed using the Severance Hospital dataset (n = 1,180) and were validated by the nationwide Korean Breast Cancer Society (KBCS) registry (n = 9,916).

Results

Despite the different distribution of ER/PR status, tumor stage, grade, and local therapies between the two datasets, similarly ER+/PR+ showed smaller size and good differentiation, ER+/PR? patients had the oldest age at diagnosis, and ER?/PR+ was associated with the youngest age at onset and grade III tumor. Single hormone receptor-positive subgroups demonstrated worse disease-related outcomes than the ER+/PR+ subgroup. These associations were confirmed by the KBCS dataset. This trend was also demonstrated in the subpopulation of 1,944 patients with Ki-67 < 14 %. Inferior survival of single receptor-positive tumors was more definite among node-positive patients even when receiving both chemo-endocrine therapies.

Conclusions

Current results suggest that the luminal A subtype is also heterogeneous and each subgroup has unique clinicopathologic characteristics. Lack of either ER or PR expression is associated with worse survival, especially among node-positive luminal A subtype.     

Androgen Receptor Expression Shows Distinctive Significance in ER Positive and Negative Breast Cancers

Background

Androgen receptor (AR), a nuclear steroid hormone receptor, is differentially expressed in breast cancer subgroups with distinct clinical implications.

Methods

To investigate the clinical significance of AR in breast cancers more precisely, the expression of AR in a large cohort of breast cancer was correlated with clinicopathological features, biomarker expression, and patients’ survival according to different molecular groupings in this study.

Results

Higher AR expression was found in ER+ (57.8 %) than in ER? (24.7 %) cancers. In the ER+ cancers, AR expression was associated with favorable clinicopathological features, including lower grade (p < .001), lower pT stage (p < .001), and positivity for PR (p < .001). It was an independent prognostic factor for longer disease-free survival, mainly in the HER2+ luminal B cancers (hazard ratio [HR] = 0.251, 95 % CI 0.065?0.972, p = .045). In ER? cancers, AR expression was associated with features distinct from basal-like breast cancer, and such features were found in molecular apocrine (MA) cancers. AR correlated with presence of extensive in situ component (p = .006) and apocrine phenotype (p < .001), HER2 (p = .026), and EGFR (p = .048), but negatively with c-kit (p = .041), CK5/6 (p < .001), CK14 (p = .002), and αB-crystallin (p = .038). However, AR expression was found only in 37.8 % of immunohistochemically defined MA. Of note, AR?MA appeared to have a trend of worse overall survival than AR+MA.

Conclusions

AR expression was different in ER+ and ER? cancers and had different clinical implications. AR alone may not be a good marker for MA subtype. Its expression in MA may have substantial prognostic implication and as such warrants further validation.     

Impact of Neoadjuvant Chemotherapy on Nodal Disease and Nodal Surgery by Tumor Subtype

Background

Neoadjuvant chemotherapy (NAC) is known to downstage disease in the breast and increase breast conservation. It can also decrease nodal disease extent. We evaluated the impact of NAC on nodal positivity, nodal burden, and nodal surgery by tumor subtype.

Methods

All cT1–4c breast cancers from 2010 to 2014 in the National Cancer Database were evaluated, comparing patients receiving NAC with those undergoing primary surgery (PS). Rates of pathologic node-negative status (pN0) and sentinel lymph node (SLN) surgery (1–5 nodes) were compared using chi-square tests, and adjusted odds ratios (OR) were estimated.

Results

Of 461,549 patients, 36,715 (8.0%) received NAC and 424,834 (92.0%) had PS. In cN0 patients, pN0 rates were higher in NAC compared with PS patients in ER?/HER2+ [93.2 vs. 79.0%, odds ratio (OR) 3.64, p < 0.001], ER?/HER2? (89.9 vs. 85.2%, OR 1.55, p < 0.001), and ER+/HER2+ (84.7 vs. 78.3%, OR 1.54, p < 0.001). Patients with cT2–3, N0 tumors had significantly higher rate of SLN surgery for NAC versus PS for each biologic subtype except for ER+/HER2? tumors, amongst which this was true only for T3 tumors. In cN1–3 patients, pN0 rates after NAC were 61.3% in ER?/HER2+, 47.7% in ER+/HER2+, 47.3% in ER?/HER2?, and 20.2% in ER+/HER2? and SLN surgery was highest in ER?/HER2+ (28.9%, p < 0.05 versus other subtypes).

Conclusion

NAC increases rates of pN0 among cN0 patients compared with PS. Among cN+ patients, 20–61% undergoing NAC convert to pN0 depending on tumor type, with lowest nodal response in ER+/HER2? disease. Use of NAC results in less extensive axillary surgery than in patients treated with PS in both cN0 and cN+ disease.

     

Effect of ASCO/CAP Guidelines for Determining ER Status on Molecular Subtype

Background

Determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is standard for predicting prognosis and determining treatment options for patients with breast cancer. In 2010, the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) issued guidelines that tumors with ≥1 % positively staining cells should be considered ER positive. Here, we determined how this cutoff relates to molecular subtype.

Methods

Clinicopathological characteristics were compared between ER-negative, ER-positive, and low-ER-staining (1–10 %) tumors using chi-square analysis with P < 0.05 defining statistical significance. Gene expression data were generated for 26 low-ER-staining tumors, and their intrinsic subtype determined. Immunohistochemistry (IHC)-defined surrogate subtypes, using the threshold of positivity defined by ASCO/CAP guidelines, were compared with molecular subtypes.

Results

Low-ER-staining tumors were clinicopathologically more similar to ER-negative than to ER-positive tumors; 88 % of low-staining tumors were basal like or HER2 enriched. Only those tumors expressing 10 % ER-positive cells were classified as luminal A subtype.

Conclusions

Under ASCO/CAP guidelines, tumors with 1–10 % ER staining would be classified as ER positive, yet most are basal like or HER2 enriched and have pathological features similar to ER-negative tumors. Clinical trials seeking to treat tumors of ER-negative basal-like and/or HER2-enriched subtypes should thus not preclude enrollment based solely on results of ER immunohistochemistry. As ER status is a critical element in the choice of treatments for patients with breast cancer, it is imperative that the most effective method for classifying tumors be developed.     

Perioperative Breast MRI Is Not Associated with Lower Locoregional Recurrence Rates in DCIS Patients Treated With or Without Radiation

Introduction

For women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS), the benefit of magnetic resonance imaging (MRI) remains unknown. Here we examine the relationship of MRI and locoregional recurrence (LRR) and contralateral breast cancer (CBC) for DCIS treated with BCS, with and without radiotherapy (RT).

Methods

A total of 2,321 women underwent BCS for DCIS from 1997 to 2010. All underwent mammography, and 596 (26 %) also underwent perioperative MRI; 904 women (39 %) did not receive RT, and 1,391 (61 %) did. Median follow-up was 59 months, and 548 women were followed for ≥8 years. The relationship between MRI and LRR was examined using multivariable analysis.

Results

There were 184 LRR events; 5- and 8-year LRR rates were 8.5 and 14.6 % (MRI), respectively, and 7.2 and 10.2 % (no-MRI), respectively (p = 0.52). LRR was significantly associated with age, menopausal status, margin status, RT, and endocrine therapy. After controlling for these variables and family history, presentation, number of excisions, and time period of surgery, there remained no trend toward association of MRI and lower LRR [hazard ratio (HR) 1.18, 95 % confidence interval (CI) 0.79–1.78, p = 0.42]. Restriction of analysis to the no-RT subgroup showed no association of MRI with lower LRR rates (HR 1.36, 95 % CI 0.78–2.39, p = 0.28). No difference in 5- or 8-year rates of CBC was seen between the MRI (3.5 and 3.5 %) and no-MRI (3.5 and 5.1 %) groups (p = 0.86).

Conclusions

We observed no association between perioperative MRI and lower LRR or CBC rates in patients with DCIS, with or without RT. In the absence of evidence that MRI improves outcomes, the routine perioperative use of MRI for DCIS should be questioned.     

Race and the Prognostic Influence of p53 in Women with Breast Cancer

Background

Prior study suggests that p53 status behaves as an independent marker of prognosis in African American (AA) women with breast cancer. We investigate whether the influence of p53 is unique to AAs or is present in other race/ethnic groups, and how this compares with known prognostic factors.

Methods

Cox regression models [hazard ratios (HRs), 95% confidence intervals (CIs)] were used to select and evaluate factors prognostic for all-cause mortality in 331 AA and 203 non-AA consecutively treated women.

Results

Statistically significant baseline prognostic factors were as follows. For AAs: stage [(III/I) HR 5.57; 95% CI 3.08?C10.09], grade [(higher/low) HR 1.55; 95% CI 1.14?C2.11], estrogen receptor (ER)/progesterone receptor (PR) status [(?/+) HR 2.01; 95% CI 1.38?C2.93], triple negative (ER?, PR?, HER2?) subtype [(+/?) HR 1.95; 95% CI 1.33?C2.85], and p53 status [(+/?) HR 1.69; 95% CI 1.10?C2.58]. For non-AAs: stage [HR 11.93; 95% CI 2.80?C50.84], grade [HR 1.61; 95% CI 0.96?C2.71], and ER/PR status [HR 2.13; 95% CI 1.19?C3.81]. There was a differential effect of race within p53 groups (P?=?0.05) and in multivariate modeling p53-positive status remained an adverse prognostic factor in AAs only [HR 1.82; 95% CI 1.04?C3.17]. Compared to non-AAs, 5-year unadjusted survival was worse for AAs overall (73.4% vs. 63.6%; P?=?0.032), and also for AAs with p53-positive status (80.3% vs. 54.2%; P?=?0.016), but not for AAs with p53-negative disease (68.4% vs. 67.9%; P?=?0.81).

Conclusions

Among women with breast cancer of different race/ethnicity, an adverse prognostic effect as a result of p53 positivity was only observed in AA women.     

Comparison of Molecular Subtyping with BluePrint, MammaPrint, and TargetPrint to Local Clinical Subtyping in Breast Cancer Patients

Purpose

To compare breast cancer subtyping with the three centrally assessed microarray-based assays BluePrint, MammaPrint, and TargetPrint with locally assessed clinical subtyping using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

Methods

BluePrint, MammaPrint, and TargetPrint were all performed on fresh tumor samples. Microarray analysis was performed at Agendia Laboratories, blinded for clinical and pathological data. IHC/FISH assessments were performed according to local practice at each institution; estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) assessments were performed on 132 samples, and Ki-67 on 79 samples.

Results

The concordance between BluePrint and IHC/FISH subtyping was 94 % for the Luminal-type, 95 % for the HER2-type, and 94 % for the Basal-type subgroups. The concordance of BluePrint with subtyping using mRNA single gene readout (TargetPrint) was 96 % for the Luminal-type, 97 % for the HER2-type, and 98 % for the Basal-type subgroups. The concordance for substratification into Luminal A and B using MammaPrint and Ki-67 was 68 %. The concordance between TargetPrint and IHC/FISH was 97 % for ER, 80 % for PR, and 95 % for HER2.

Conclusions

The implementation of multigene assays such as TargetPrint, BluePrint, and MammaPrint may improve the clinical management of breast cancer patients. High discordance between Luminal A and B substratification based on MammaPrint versus locally assessed Ki-67 or grade indicates that chemotherapy decisions should not be based on the basis of Ki-67 readout or tumor grade alone. TargetPrint serves as a second opinion for those local pathology settings where high-quality standardization is harder to maintain.     

High Volumetric Breast Density Predicts Risk for Breast Cancer in Postmenopausal,but not Premenopausal,Korean Women

Purpose

We investigated the association between mammographic breast density and breast cancer risk in Korean women according to menopausal status and breast cancer subtypes.

Methods

We enrolled 677 patients diagnosed with breast cancer and 1,307 healthy controls who participated in screening mammography at the National Cancer Center. Breast density was estimated using volumetric breast composition measurement.

Results

Of the total population, 1,156 (58.3 %) women were postmenopausal. The risk of breast cancer increased progressively with the increment of volumetric density grade (VDG) in postmenopausal women (p < 0.001). High breast density (VDG 4) was significantly associated with breast cancer compared with low breast density (VDG 1/2) regardless of body mass index. However, the association with parity and history of hormone replacement therapy (HRT) was only found in those with ≥2 children and those not receiving HRT. Breast density was positively associated with breast cancer risk regardless of histologic grade, tumor size, lymph node involvement, Ki67 index, and hormone receptor status. The association was more prominent in human epidermal growth factor receptor 2 (HER2)-positive tumors (VDG 1/2 vs. VDG 4 for HER2 normal, odds ratio [OR] 2.21, 95 % confidence interval [CI] 1.28–3.83, p < 0.001; for HER2 positive, OR 8.63, 95 % CI 3.26–22.83, p = 0.001; P _{heterogeneity} = 0.030). However, no significant association was found between breast density and breast cancer risk in premenopausal women except for those with large-sized tumors (>2 cm) and a Ki67 index >15 %.

Conclusion

High volumetric breast density is significantly associated with the risk of breast cancer in postmenopausal women; however, these relationships were not found in premenopausal women.     

Treatment Strategies in Octogenarians with Early-Stage,High-Risk Breast Cancer

Background

Octogenarians with early-stage breast cancer often have low-risk tumor biology. However, optimal treatment strategies for those with high-risk biology remain unclear.

Methods

We reviewed the records of women ages 80–89 years with biopsy-proven, Stage I–II invasive breast cancer who were referred for surgical evaluation from January 2001 through December 2010. High-risk was defined as human epidermal growth factor receptor-positive (HER2+), triple-negative (TN), or histologic grade 3 disease.

Results

Among 178 patients, 40 (22%) were high-risk: 12 were grade 1–2 (10 HER2 + , 2 TN); 28 were grade 3 (7 HER2+, 6 TN, 15 estrogen receptor-positive (ER+)/HER2?). The high-risk group had larger tumors and more often had ductal histology and lymphovascular invasion than the low-risk group and was more likely to undergo mastectomy (18 vs. 5%, p = 0.02), radiotherapy (55 vs. 36%, p = 0.03), and chemotherapy (10 vs. 0%, p = 0.002). Endocrine therapy use was similar among ER+ patients in both groups. The four patients in the high-risk group given chemotherapy were HER2+ and received trastuzumab-based regimens, without any reported toxicities. At median follow-up of 67 months, 10% of the high-risk group had a recurrence (3 distant-only, 1 simultaneous locoregional and distant in a patient treated with mastectomy without radiotherapy).

Conclusions

Tailored locoregional and systemic therapy resulted in low incidence of failure in these octogenarians with high-risk cancers with low morbidity. Modern adjuvant therapies should be considered for elderly women with high-risk cancers in the absence of significant comorbidities.

     

Update on DCIS Outcomes from the American Society of Breast Surgeons Accelerated Partial Breast Irradiation Registry Trial

Background

Since the initial reports on use of MammoSite accelerated partial breast irradiation (APBI) for treatment of ductal carcinoma in situ (DCIS), additional follow-up data were collected. We hypothesized that APBI delivered via MammoSite would continue to be well tolerated, associated with a good cosmetic outcome, and carry a low risk for recurrence in patients with DCIS.

Materials and Methods

From 2002–2004, 194 patients with DCIS were enrolled in a registry trial to assess the MammoSite. Follow-up data were available for all 194 patients. Median follow-up was 54.4 months; 63 patients had at least 5 years of follow-up. Data obtained included patient-, tumor-, and treatment-related factors, and recurrence incidence.

Results

Of the 194 patients, 87 (45%) had the MammoSite placed at lumpectomy; 107 patients (55%) had the device placed postlumpectomy. In the first year of follow-up, 16 patients developed a breast infection, though the method of device placement was not associated with infection risk. Also, 46 patients developed a seroma that was associated with applicator placement at the time of lumpectomy (P = 0.001). For patients with at least 5 years of follow-up, 92% had favorable cosmetic results. There were 6 patients (3.1%) who had an ipsilateral breast recurrence, with 1 (0.5%) experiencing recurrence in the breast and axilla, for a 5-year actuarial local recurrence rate of 3.39%.

Conclusions

During an extended follow-up period, APBI delivered via MammoSite continued to be well tolerated for patients with DCIS. Use of this device may make lumpectomy possible for patients who would otherwise choose mastectomy because of barriers associated with standard radiation therapy.     

A Novel Morphologic-Molecular Recurrence Predictive Model Refines Traditional Prognostic Tools for Invasive Breast Carcinoma

Background

Histologic grade, TNM stage, and Nottingham Prognostic Index are traditional prognostic tools for breast cancer. “IHC-molecular” classification of breast cancer can also identify patients at different recurrence risks and provides insight into cancer therapy. However, cancers in each group are heterogeneous. A model based on the comprehensive analysis of morphologic features and molecular subtype was constructed to predict recurrence and refine these traditional prognostic tools.

Methods

Morphologic features including histologic grade, fibrotic focus, extensive intraductal component, lymphocytic infiltrate, lymphovascular invasion, tumor necrosis, tumor margin and TNM stage, and molecular subtypes approximated by immunohistochemistry were analyzed in 633 patients with invasive breast carcinoma (excluding those with HER2 targeted therapy). Significant independent predictors for recurrence included: high histologic grade (p = 0.004), presence of lymphovascular invasion (p = 0.004), fibrotic focus (p = 0.020), mild lymphocytic infiltrate (p = 0.013), high TNM stage (p < 0.001), and HER2-overexpressing (p = 0.004) and basal-like (p < 0.001) molecular subtypes. A morphologic-molecular recurrence predictive model based on these features was useful in recurrence prediction, independent of treatment modalities, and was able to refine the traditional prognostic tools of histologic grade, TNM stage, and Nottingham prognostic index, particularly for intermediate-risk groups, and to refine the luminal group molecular subtypes. Such findings were reproducible with a validation cohort.

Conclusion

TNM stage, histologic grade, lymphovascular invasion, fibrotic focus, mild lymphocytic infiltrate, HER2-overexpressing and basal-like molecular subtypes were important independent recurrence risk factors for breast cancer. This morphologic-molecular model was robust in recurrence prediction and refined recurrence risk stratified by the traditional prognostic parameters, independent of treatment modalities.     

乳腺导管原位癌、微浸润癌及浸润性癌临床病理指标表达差异分析

目的：比较乳腺导管原位癌（DCIS）、导管原位癌伴微浸润（DCIS-MI）及浸润性乳腺癌（IDC）临床病理及免疫组化特征。方法回顾性分析2008至2013年的214例乳腺癌患者的临床病理资料,其中DCIS 66例,DCIS-MI 48例,IDC 100例。根据免疫组化结果分为4组：Luminal-A [ER（＋）和／或 PR（＋）,HER2（－）],Luminal-B [ER（＋）和／或 PR（＋）,HER2（＋）],HER2（＋）型[ER（－）,PR（－）,HER2（＋）],和三阴型[ER（－）,PR（－）,HER2（－）]。结果从DCIS、DCIS-MI到IDC,肿瘤大小逐渐增加（P＜0．001）。IDC腋窝淋巴结阳性率高于DCIS和DCIS-MI（P＜0．001）。ER、PR、HER2阳性表达在纯DCIS、DCIS-MI与IDC之间的表达显著差异,P值均小于0．05。随着浸润的发展,Luminal-like 型比例下降,而HER2＋型和三阴型的比例增加（P＝0．016）。Ki-67指数分别为DCIS（10．4±12．9）％,DCIS-MI（13．9±16．3）％,IDC（43．9±26．4）％（P＜0．001）。结论在DCIS、DCIS-MI、IDC中不同亚型的分布以及各自的临床病理特点表明它们之间存在很大不同。     

Basal Subtype,as Approximated by Triple-Negative Phenotype,is Associated with Locoregional Recurrence in a Case–Control Study of Women with 0–3 Positive Lymph Nodes After Mastectomy

Purpose

Basal subtype, as approximated by the triple-negative phenotype (ER–PR–Her2?), has correlated with higher LRR in recent studies. Indications for postmastectomy RT (PMRT) in women with 0–3 positive lymph nodes remain unclear. We evaluated the importance of biologic subtype in a cohort of women with LRR after mastectomy.

Methods

We identified 22 women with 0–3 positive lymph nodes at our institution who were initially treated with mastectomy (without post-mastectomy radiation), suffered LRRs, and had paraffin-embedded tissue blocks from the primary mastectomy specimen available for staining. None of these women received PMRT. We case–control matched these to 29 women with 0–3 positive nodes who had mastectomy (no PMRT) and remained without evidence of disease at last follow-up and had available primary specimens for processing. We matched controls for age (±3 years) and follow-up duration (<5 year vs. more). Paraffin-embedded specimens were used to construct a triple-redundant tissue microarray. We used conditional logistic regressions to study the association between each predictor and LRR. Results were summarized based on odds ratio (OR).

Results

On univariate analysis, ER+, PR+, or the combination was strongly associated with lower odds of LRR. Basal subtype, as approximated by ER–PR–Her2? (TN), was associated with higher LRR (OR 8.5, p = 0.048). Use of chemotherapy also was associated with lower LRR (OR 0.126, p = 0.0073).

Conclusions

Our data are concordant with reports from others demonstrating that TN phenotype is associated with higher LRR and can be considered along with other predictors of LRR when selecting women for PMRT.     

Response to HER-2 Pulsed DC1 Vaccines is Predicted by Both HER-2 and Estrogen Receptor Expression in DCIS

Background

Patients with estrogen-independent (ER^neg) human epidermal growth factor receptor-2 (HER-2)-positive ductal carcinoma in situ (DCIS) treated with lumpectomy alone or lumpectomy and radiation are at increased risk of developing subsequent breast cancer events.

Methods

Thirty-eight patients with HER-2 expressing DCIS received a HER-2 pulsed autologous dendritic cell (DC1) vaccine administered over 4–6 weeks before surgical resection. HER-2 and estrogen receptor (ER) expression were determined by immunohistochemistry. In 35 patients, CD4^pos T-cell sensitization to HER-2 peptides was identified by ELISPOT. In 19 patients, CD8^pos T-cell responses were identified by ELISA. Clinical and immune responses postvaccination were compared between intermediate-expressing HER-2 (2+) and high-expressing HER-2 (3+) patients, as well as ER^neg and estrogen-dependent (ER^pos) patients.

Results

There was no significant difference in immune response after HER-2 vaccination in patients with HER-2 (2+) and (3+) tumors or ER^neg and ER^pos tumors. Complete tumor regression rates were similar in patients with HER-2 (2+) and (3+) DCIS. Overall, clinical response rates were similar in patients with ER^neg and ER^pos DCIS, but complete tumor regression was significantly more common in patients with ER^neg DCIS.

Conclusions

Despite equivalent immune responses after vaccination in patients with HER-2 (2+), HER-2 (3+), ER^neg and ER^pos DCIS, HER-2 pulsed DC1 induces more complete responses in patients with ER^neg DCIS. These data provide a rationale for developing vaccinations to reduce recurrence in patients with ER^neg DCIS for whom there are currently limited adjuvant options.     

Effect of MRI on the Management of Ductal Carcinoma In Situ of the Breast

Introduction

The accuracy of breast magnetic resonance imaging (MRI) for detection of ductal carcinoma in situ (DCIS) has prompted recommendations for its routine preoperative use, but its clinical benefit is debated. We reviewed our experience with MRI in DCIS patients to assess the utility of MRI for surgical planning.

Methods

DCIS patients (2008–2010) were identified through a prospectively maintained database and grouped into MRI and no-MRI groups. The rates of additional biopsies, altered surgical management, and reoperation were compared. Additionally, DCIS size ascertained by mammography, MRI, and final pathology was compared.

Results:

Of 352 DCIS patients, 217 received MRI and 135 did not. The type of initial operation and number of reoperations were similar between the two groups, but successful breast conservation was more frequent in the no-MRI group (p = 0.06). The additional biopsy rate was 38 % in the MRI group versus 7 % in the no-MRI group; ≥2 additional biopsies were performed in 18 % of the MRI group and 2 % of the no-MRI group (p < 0.0001). These yielded a cancer diagnosis in 26 % of MRI and 33 % of no-MRI patients (p = 0.73). MRI was not superior to mammogram in detecting size of DCIS lesions preoperatively; 52 % of mammograms were accurate (within 1 cm) compared with 41 % of MRIs.

Conclusions

DCIS patients who undergo preoperative breast MRI are far more likely to undergo additional biopsies. Unless these can be demonstrated to lead to improved long-term outcomes, the utility of routine preoperative MRI in DCIS patients remains questionable.     

Locoregional Recurrence and Survival Outcomes by Type of Local Therapy and Trastuzumab Use Among Women with Node-Negative,HER2-Positive Breast Cancer

Background

While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy.

Methods

Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group.

Results

Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p < 0.001) and trastuzumab therapy (50 vs 57 %, p = 0.04). The 5-year outcomes in women treated with BCT compared with mastectomy were: LRRFS 98.0 versus 98.3 % (p = 0.88), BCSS 97.2 versus 96.1 % (p = 0.70), and OS 95.5 versus 93.4 % (p = 0.19). Trastuzumab was associated with similar LRRFS and improved OS in both local treatment groups.

Conclusions

BCT is safe in the population of women with pT1–2, N0, HER2+ breast cancer, providing high rates of locoregional control and survival equivalent to mastectomy. Trastuzumab was associated with improved survival in both groups.     

Should Ductal Carcinoma-in-situ (DCIS) Be Removed from the ASTRO Consensus Panel Cautionary Group for Off-protocol Use of Accelerated Partial Breast Irradiation (APBI)? A Pooled Analysis of Outcomes for 300 Patients with DCIS Treated with APBI

Purpose

To analyze outcomes in patients with ductal carcinoma-in-situ (DCIS) treated with accelerated partial breast irradiation (APBI) within a pooled set of patients.

Methods

A total of 300 women with DCIS underwent APBI between April 1993 and November 2010 as part of American Society of Breast Surgeons MammoSite Registry Trial (n = 192) or at William Beaumont Hospital (n = 108). Patients with pure DCIS <3 cm (n = 125) were assigned to the cautionary risk group per American Society of Radiation Oncology consensus panel guidelines for off-protocol use of APBI and analyzed compared to a pooled invasive suitable (n = 653) risk group and pooled invasive suitable/cautionary (n = 1,298) risk group.

Results

The rate of ipsilateral breast tumor recurrence (IBTR) for all 300 DCIS patients was 2.6 % at 5 years with no regional recurrences, while cause-specific survival was 99.5 % and overall survival (OS) was 96.4 %. When comparing the cautionary DCIS group to the invasive suitable/cautionary group, no difference in IBTR was noted (2.6 vs. 3.1 %, P = 0.90) with significant improvements in distant metastases (0 vs. 2.5 %, P = 0.05), disease-free survival (98.5 vs. 94.4 %, P = 0.05), and OS (95.7 vs. 90.8 %, P = 0.03) noted for DCIS patients. When comparing cautionary DCIS patients to invasive suitable patients, no difference in IBTR were noted (2.6 vs. 2.4 %, P = 0.76), while improved OS for DCIS patients was noted (95.7 vs. 90.9 %, P = 0.02).

Conclusions

This analysis of the largest cohort of patients with DCIS treated with APBI supports previously reported excellent outcomes; as a result of small numbers of events, further data are necessary to confirm these findings.     

Predictors of Treatment with Mastectomy, Use of Sentinel Lymph Node Biopsy and Upstaging to Invasive Cancer in Patients Diagnosed with Breast Ductal Carcinoma In situ (DCIS) on Core Biopsy

Background

There are few established indications for sentinel lymph node biopsy (SLNB) in breast ductal carcinoma in situ (DCIS). This study examines factors contributing to the high rate of SLNB in DCIS in Alberta, Canada.

Methods

Patients who underwent definitive surgery from January 2009 to July 2011 for DCIS diagnosed on preoperative core-needle biopsy were identified using a provincial synoptic operative report database (WebSMR). The relationship between baseline patient and tumor characteristics and treatment with total mastectomy (TM), use of SLNB, and upstaging were examined.

Results

There were 394 patients identified in the study cohort. Mean age was 57 years, and average preoperative tumor size was 3 cm. Overall, 148 patients (37.6 %) underwent TM; predictors were preoperative tumor size [odds ratio (OR), 1.92 per 1-cm increase in size; 95 % CI 1.65–2.24] and surgeon. Upstaging to invasive cancer at surgery occurred in 23 %, predicted only by preoperative tumor size (OR 1.14 per 1 cm; 95 % CI 1.03–1.27). SLNB was performed in 306 patients overall (77 %) and 140 of those treated with BCS (61 %). Predictors of SLNB were larger preoperative tumor size (OR 1.55 per 1 cm; 95 % CI 1.18–2.04) and the surgeon. In patients treated with BCS, 3 patients who were upstaged had positive SLNs (>0.2 mm), and no patients with DCIS had a positive SLN.

Conclusions

SLNB use is high in patients undergoing BCS for DCIS. Tumor size and the operating surgeon predicted SLNB use. Despite a 23 % upstaging rate, the rate of clinically significant positive SLNs in patients treated with BCS is low, supporting omission of upfront SLNB.     

Decreasing Use of Axillary Dissection in Node-Positive Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) may downstage axillary disease in node-positive breast cancer. Several clinical trials have shown that sentinel lymph node (SLN) surgery after NAC is feasible for these patients. We sought to evaluate the use of SLN surgery and ALND in cN1 patients undergoing NAC.

Methods

We identified all patients with biopsy-proven cN1 breast cancer treated with NAC at our institution between January 2009 and December 2017. Approximated biologic subtype was determined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. Cochran–Armitage trend and Chi square tests were used for statistical analysis.

Results

Of 430 cN1 patients treated with NAC, 93 (22%) underwent SLN surgery only, 100 (23%) underwent SLN and ALND, and 237 (55%) underwent ALND only. The use of SLN surgery (±?ALND) increased from 28% in 2009 to 86% in 2017 (p?<?0.001), while the performance of ALND decreased from 100% in 2009 to 38% in 2017 (p?<?0.001). Among SLN+ patients who underwent ALND, disease was limited to the SLNs in 25/73 (34%) patients. The nodal pathologic complete response rate was 46% and varied by tumor subtype (p?<?0.001). Among patients undergoing SLN surgery, ALND was avoided in 48% of patients overall and varied by biologic subtype: 55% ER?/HER2+, 61% ER+/HER2+, 62% ER?/HER2?, and 31% ER+/HER2? (p?=?0.001). With short-term follow-up, no nodal recurrences have occurred in patients without ALND.

Conclusions

We observed a significant shift in axillary surgery for cN1 breast cancer patients treated with NAC, with increasing use of SLN surgery to assess nodal treatment response, and decreasing use of ALND.

     

HER2 Expression in Carcinomas of the True Cardia (Siewert Type II Esophagogastric Junction Carcinoma)

Objectives

To evaluate the HER2 status in patients with Siewert type II esophagogastric junction carcinoma.

Background

Trastuzumab is now approved for use in the treatment of human epidermal growth factor receptor 2 (HER2)-positive unresectable metastatic gastric or esophagogastric junction (EGJ) carcinoma. Several studies have evaluated HER2 status in EGJ carcinoma, but none has addressed the implication of HER2 positivity in patients with Siewert type II EGJ carcinoma.

Methods

We retrospectively evaluated the frequency of HER2 positivity in a large single-center cohort of 208 patients with Siewert type II tumors. The relations between HER2 expression and the outcomes and other clinicopathologic features were examined.

Results

Overall, 18.2 % (38/208) of patients in our cohort had HER2-positive tumors. HER2 positivity was associated only with differentiated carcinomas. The 5-year overall survival (OS) rate was 58.7 %. The 5-year OS rates in the patient groups with HER2-negative and HER2-positive tumors were 61.2 and 48.5 %, respectively. There was no significant difference between the groups. Recurrence in the liver was observed in 23.7 % patients of the HER2-positive group and 7.6 % patients of the HER2-negative group. Multivariate analysis to identify the risk factors for liver recurrence revealed only HER2 positivity (p = 0.0155) as an independent predictive factor.

Conclusions

HER2 positivity is a powerful predictor of liver recurrence in patients with Siewert type II EGJ carcinoma. Use of trastuzumab in combination with chemotherapy in an adjuvant setting can be a potentially useful therapeutic strategy to prevent hepatic recurrence in patients with resectable EGJ adenocarcinoma showing HER2 overexpression.