Prognosis of Japanese Breast Cancer Based on Hormone Receptor and HER2 Expression Determined by Immunohistochemical Staining

BACKGROUND: We classified Japanese breast cancer patients based on estrogen receptor (ER), progesterone receptor (PR), and HER2 protein expression and compared their prognoses. METHODS: We compared the background and prognostic factors of 600 patients with breast cancer who were assigned to the following groups: luminal A (ER + and/or PR + and HER2-; n = 431; 71.8%), luminal B (ER + and/or PR + and HER2 + ; n = 27; 4.5%), HER2 (ER-, PR-, and HER2 + ; n = 39; 6.5%) and basal-like (BBC; ER-, PR-, and HER2-; n = 103; 17.2%). RESULTS: Background factors did not significantly differ among the groups. Disease-free survival rates were significantly lower for the luminal B, HER2, and BBC subtypes than for the luminal A subtype. Cancer tended to recur earlier and overall survival was significantly lower for the BBC than for the luminal A and HER2 subtypes. Overall survival rates for the luminal B, HER2, and luminal A subtypes were comparable. CONCLUSIONS: The subtype distribution for Japanese and Caucasian patients was comparable. The prognosis for the BBC subtype was poorest among all subtypes. Breast cancer tended to recur earlier for the luminal B and HER2 subtypes than for the luminal A subtype; however, overall survival did not significantly differ among them.     

Prognostic Value of Breast Cancer Subtypes,Ki‐67 Proliferation Index,Age, and Pathologic Tumor Characteristics on Breast Cancer Survival in Caucasian Women

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well‐established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER‐/PR‐/HER2‐) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki‐67 proliferation index (Ki‐67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000‐late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan–Meier curve. ER/PR/HER2 status, grade, tumor‐node‐metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki‐67PI was analyzed between ER/PR/HER2 groups using the Kruskal–Wallis, Mann–Whitney U‐tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1–16 times more likely to die than patients with stages IA‐B and IIA disease, respectively (95% CI 1.17–3.81 through 9.68–28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki‐67PI between ER/PR/HER2 subtypes, p < .001, but Ki‐67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki‐67 proliferation index are not.     

Is the TNM Staging System for Breast Cancer Still Relevant in the Era of Biomarkers and Emerging Personalized Medicine for Breast Cancer – An Institution's 10‐year Experience

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000–2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five‐group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty‐two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non‐TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01–1.97; Stage III = HR 3.96, 95% CI 2.68–5.88; Stage IV = HR 27.25, 95% CI 16.84–44.08), and age (HR 1.05, 95% CI 1.04–1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88–5.04, Stage IV = HR 24.36, 95% CI 13.81–42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).     

Different Distribution of Breast Cancer Subtypes in Breast Ductal Carcinoma in situ (DCIS), DCIS with Microinvasion, and DCIS with Invasion Component

Background

Breast ductal carcinoma in situ with microinvasion (DCIS-Mi) is considered to be the interim stage in the progression from DCIS to invasive breast cancer (IDC). Cases that exceed DCIS-Mi but still do not fulfill the diagnostic criteria of IDC often are observed. We define those cases as DCIS with invasion component (DCIS-I), and attempt to study the differences of clinicopathological features and immunohistochemical-based subtypes among DCIS, DCIS-Mi, and DCIS-I.

Methods

In this retrospective study, 550 consecutive DCIS patients were recruited, 271 (49.3%) cases were diagnosed as pure-DCIS, 67 as DCIS-Mi, and 212 as DCIS-I. They were categorized into four groups: luminal-A (ER+ and/or PR+, HER2?), luminal-B (ER+ and/or PR+, HER2+), ERBB2+ (ER?, PR?, HER2+), and basal-like (ER?, PR?, HER2?).

Results

DCIS-Mi and DCIS-I patients tended to have larger tumors with highly graded nuclear (P = 0.011 for size; P < 0.0001 for nuclear grade). The proportion of luminal-like tumors decreased, whereas ERBB2+ and basal-like tumors increased in DCIS-I/DCIS-Mi compared with pure-DCIS (P = 0.039). Although the HER2-positive tumors displayed a stable proportion among DCIS subgroups, the essences of them were varying. In pure-DCIS, luminal-B was the major subtype of HER2-positive tumors (luminal-B vs. ERBB2+, 19% vs. 14.6%), whereas in DCIS-I, the proportion of luminal-B decreased vastly (luminal-B vs. ERBB2+, 12.8% vs. 23.5%). DCIS-I had a worse relapse-free survival outcome compared with pure-DCIS.

Conclusions

Different distribution of subtypes and distinctive characteristics among DCIS, DCIS-Mi, and DCIS-I indicate that they are distinct entities. Further studies with larger sample size are needed to replicate our observations.     

Is There a Correlation Between Breast Cancer Molecular Subtype Using Receptors as Surrogates and Mammographic Appearance?

Background

The identification of distinct molecular subtypes has changed breast cancer management. The correlation between mammographic appearance and molecular subtype for invasive breast cancer has not been extensively studied.

Methods

A retrospective review of our prospectively collected database was performed to evaluate the mammographic appearance and molecular subtypes of all cases of invasive breast cancers diagnosed between 2003 and 2010.

Results

There were 985 cases of invasive breast cancer with complete data on receptor status and mammographic appearance. The most common mammographic finding was a mass (61 %), and the most common molecular subtype was ER/PR positive, HER2 negative (71 %). On univariate analysis, race, stage, and histology were all significantly associated with molecular subtype. On multivariate analysis, the luminal molecular type was associated with architectural distortion [odds ratio (OR) 4.3, 95 % CI 1.3–14.1]; HER2 positive cancers, either with or without ER/PR expression, were more likely to be associated with mammographic calcifications (OR 2.8 and 3.1, respectively; 95 % CI 1.7–4.8 and 1.7–5.5); and triple negative cancers were most likely to be associated with a mammographic mass (OR 2.5; 95 % CI 1.4–4.4).

Conclusions

We observed several characteristic associations between molecular subtype and mammographic appearance. Improved understanding of these associations may help guide clinical decision making and provide information about underlying tumor biology.     

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.     

Survival and clinicopathological characteristics of breast cancer patient according to different tumour subtypes as determined by hormone receptor and Her2 immunohistochemistry. a single institution survey spanning 1998 to 2010

As far as recent breast cancer molecular subtype classification is concerned, much work has dealt with clinical outcomes for triple negative and Her2 patients. Less is known about the course of patients in the remaining subtypes. Molecular classification based on immunohistochemistry is widely available and correlates well with genetic microarray assessment, but at a lower cost. The aim of our investigation was to correlate immunohistochemical subtypes of breast cancer with clinical characteristics and patient outcomes. Since 1998, 1167 patients operated for 1191 invasive breast tumours were included in our database. Patients were regularly followed up until March 2010. Disease-free survival, overall mortality, and breast cancer-specific mortality at 5 years were calculated for the cohort. 72% of tumours were ER+PR±HER2- group, 13% triple negative (ER-PR-HER2-), 10% ER+PR±HER2+ group, and 5% Her2 (ER-PR-HER2+). Cancer-specific survival was 94.2% for the ER+PR+HER2- subtype, 84.8% for the Her2 subtype, 83.3% for the ER+PR-HER2- subtype, and 78.6% for triple negatives. Distant metastases prevalence ranged from 7% to 22% across subtypes, increasing stepwise from ER+PR+HER2-, ER+PR+HER2+, ER+PR-HER2-, ER+PR-HER2+, ER-PR-HER2+ through triple negative. Small, low-grade tumours with low axillary burden were more likely to belong to the ER+PR±HER2- group. Conversely, larger high-grade tumours with significant axillary burden were more likely to belong to Her2 or triple negative groups. ER+PR±HER2- group patients with negative PR receptors performed more like Her2 or triple negative than like the rest of ER+PR±HER2± groups patients. Molecular classification of breast tumours based only on immunohistochemistry is quite useful on practical clinical grounds, as expected. ER+PR±HER2- group patients with negative PR receptors seem to be at high risk and deserve further consideration.     

Prognostic Value of PD‐L1 in Breast Cancer: A Meta‐Analysis

Programmed cell death 1 ligand 1 (PD‐L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD‐L1 and breast cancer survival remains unclear. Here, we present the first meta‐analysis to investigate the prognostic value of PD‐L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD‐L1 expression and breast cancer survival. Fixed‐ and random‐effect meta‐analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD‐L1 overexpression was found in 25.8% of breast cancer patients. PD‐L1 (+) associated with several high‐risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2‐rich and Basal‐like p = 0.000). PD‐L1 overexpression had no significant impact on metastasis‐free survival (HR 0.924, 95% CI = 0.747–1.141, p = 0.462), disease‐free survival (HR 1.122, 95% CI = 0.878–1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640–1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010–2.451, p = 0.045). PD‐L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD‐L1 assessment assay and well‐controlled clinical trials are warranted to clarify its prognostic and therapeutic value.     

Mammographic Density,Estrogen Receptor Status and Other Breast Cancer Tumor Characteristics

Abstract: The aim of this study was to examine the relationship between mammographic density and histological characteristics of breast tumors within a case–control study population. This study was an expansion of a large size case–control study examining the relationship between breast density and breast cancer risk. Percent and area of breast density was assessed in 370 invasive breast cancer cases and 1904 age‐matched controls, using a computer‐assisted method. Associations between breast density and estrogen receptor (ER) status, histological grade, histological size, lymph node status, vascular invasion, disease extent, and Nottingham Prognostic Index were evaluated, using logistic regression. Women with 50% or greater mammographic density have a 2.63‐fold risk (95% confidence interval [95% CI] = 1.78–3.87; p < 0.001) of developing breast cancer compared to women with less than 10% density. Increase in every category of percentage of breast density is also associated with a 1.45‐fold risk in developing ER positive tumors relative to ER negative tumors (odds ratio [OR] = 1.02; 95% CI = 1.00–1.04; p = 0.048), and increase in every quartile of absolute area of density is associated with a 1.48‐fold ER positive breast cancer risk [95% CI = 1.06–2.07; p = 0.020]. Furthermore, breast density was found to be associated with specifically ER positivity, invasion as well as invasion with in situ, histological grades 1 and 2, tumor size larger than 1.1 cm, lack of vascular invasion, lymph node positivity and negativity, and NPI less than 4.0. After stratifying the data according to mode of diagnosis, the relationship became slightly stronger in the interval cancer group. Similar results were in observed using percent density and absolute density readings. Mammographic density was a stronger risk factor for ER positive [OR = 2.94; 95% CI = 1.94–4.43; p < 0.001] than ER negative cancers when comparing breasts with greater than 50% dense region to those with less than 10% density. No other tumor characteristic had a significant correlation with breast density. These results suggest that mammographic percent density may be more strongly related to ER positive than ER negative breast cancer, but otherwise is a risk factor for breast cancer independent of other tumor characteristics.     

Risk of Positive Sentinel Lymph Node After Neoadjuvant Systemic Therapy in Clinically Node-Negative Breast Cancer: Implications for Postmastectomy Radiation Therapy and Immediate Breast Reconstruction

Background

Residual axillary lymph node involvement after neoadjuvant systemic therapy (NST) is the determining factor for postmastectomy radiation therapy (PMRT). Preoperative identification of patients needing PMRT is essential to enable shared decision-making when choosing the optimal timing of breast reconstruction. We determined the risk of positive sentinel lymph node (SLN) after NST in clinically node-negative (cN0) breast cancer.

Methods

All cT1-3N0 patients treated with NST followed by mastectomy and SLNB between 2010 and 2016 were identified from the Netherlands Cancer Registry. Rate of positive SLN for different breast cancer subtypes was determined. Logistic regression analysis was performed to determine correlated clinicopathological variables with positive SLN.

Results

In total 788 patients were included, of whom 25.0% (197/788) had positive SLN. cT1-3N0 ER+HER2+, cT1-3N0 ER−HER2+ , and cT1-2N0 triple-negative patients had the lowest rate of positive SLN: 7.2–11.5%, 0–6.3%, and 2.9–6.2%, respectively. cT1-3N0 ER+HER2− and cT3N0 triple-negative patients had the highest rate of positive SLN: 23.8–41.7% and 30.4%, respectively. Multivariable regression analysis showed that cT2 (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.01–3.96), cT3 (OR 2.56; 95% CI 1.30–5.38), grade 3 (OR 0.44; 95% CI 0.21–0.91), and ER+HER2− subtype (OR 3.94; 95% CI 1.77–8.74) were correlated with positive SLN.

Conclusions

In cT1-3N0 ER+HER2+, cT1-3N0 ER−HER2+, and cT1-2N0 triple-negative patients treated with NST, immediate reconstruction can be considered an acceptable option due to low risk of positive SLN. In cT1-3N0 ER+HER2− and cT3N0 triple-negative patients treated with NST, risks and benefits of immediate reconstruction should be discussed with patients due to the relatively high risk of positive SLN.

     

Heterogeneity of Breast Cancer Clinical Characteristics and Outcome in US Black Women—Effect of Place of Birth

Breast cancer mortality in black women is disproportionately high; reasons for this phenomenon are still unclear. In addition to socioeconomic factors, the biology of the tumor may play a role. We analyzed 1,097 incident invasive breast cancer cases diagnosed between 2000 and 2010 in black US women from Long Island and Brooklyn. Thirty‐five percent of women had an estrogen receptor (ER) negative tumor, 46% a progesterone receptor (PR) negative tumor. ER, PR negative tumors were diagnosed at an earlier age (55.8 versus 55.3 years), at a later stage (p = 0.06), were larger in size (p = 0.04), and more frequently treated with neo‐adjuvant chemotherapy (p = 0.06) than ER, PR positive tumors. Determinants of shorter survival were: ER, PR negativity (HR: 2.2, 95% CI: 1.4–3.4), age, and stage at diagnosis (HR: 2.0; 95% CI: 1.5–2.7). ER, PR negative breast cancer born outside of the US experienced a significantly worse survival than ER, PR negative women who were born in the US. ER, PR negative tumors in black women born outside the US, mainly in the Caribbean, are biologically more aggressive than the same size and age‐matched tumors in black women born in the US. Our study suggests that environmental exposures in the country of origin may impact on host cancer interactions and cancer outcome.     

Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab

PurposeThe aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab.MethodsMedical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively.ResultsMedian follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER− and PR−) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33–8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33–8.71) were significant risk factors for development of brain metastasis as the first site of recurrence.ConclusionsIn patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER− and PR−) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.     

Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women: age-specific prevalence and survival

BACKGROUND: Breast cancer is currently regarded as a heterogeneous disease classified into various molecular subtypes using gene expression analysis. These molecular subtypes include: basal cell-like, Her-2/neu, luminal A, and luminal B. OBJECTIVES: To analyze the prevalence and clinicopathologic associations for molecular breast cancer subtypes in premenopausal and postmenopausal African-American women. DESIGN: A retrospective analysis of all African-American women diagnosed with breast cancer from 1998 to 2005, who had assessable data for ER, PR, and Her-2/neu status. Molecular subtype classification was done based on immunohistochemical surrogates for ER, PR, and Her-2/neu status obtained from Howard University tumor registry for each patient. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-), and Her-2/neu (ER-, PR-, and HER2+). OUTCOME MEASURES: We analyzed the prevalence of molecular breast cancer subtypes in a population of African-American women and determined their associations with patient demographics and clinicopathologic variables: node status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival. RESULTS: The luminal A subtype was the most prevalent in our study sample (55.4%) compared with (11.8%) luminal B, (21.2%) basal cell-like, and (11.6%) Her-2/neu subtypes. The molecular subtypes did not differ by menopausal status. However, when stratified into age-specific groups, the basal cell-like subtype (57.1%) was the most prevalent in the age group <35 y compared with luminal A, luminal B, and Her-2/neu subtypes at 25.0%, 14.3%, and 3.6%, respectively. The basal cell-like subtype also showed an age-specific bimodal distribution with a peak in the <35 y and 51 to 65 y age groups. The basal cell-like and the Her-2/neu subtypes showed an increased association with clinicopathologic variables portending a more aggressive clinical course when compared with luminal A subtype. A paradoxical inverse relationship between the expression of p53 and Bcl-2 protooncoprotein was noted in the molecular subtypes. Breast cancer-specific survival differed significantly among the molecular subtypes (P < 0.04), with the basal cell-like and Her-2/neu subtypes having the poorest outcome. CONCLUSIONS: The high prevalence of the basal cell-like subtype in the young premenopausal African-American women aged <35 y could be a contributory factor to the poorer prognosis of breast cancer observed in this cohort of patients.     

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.     

Estrogen Receptor,Progesterone Receptor,and HER2 Status Predict Lymphovascular Invasion and Lymph Node Involvement

Background

The ACOSOG Z0011 trial demonstrated that axillary dissection (ALND) is not necessary for local control or survival in women with T1/2cN0 cancer undergoing breast-conserving therapy. There is concern about applying these results to triple-negative (TN) cancers secondary to their high local-recurrence (LR) rate. We examined the frequency of lymphovascular invasion (LVI) and nodal metastases in TN cancers to determine whether ALND can be safely avoided in this subtype.

Methods

Data were obtained from a database of patients with invasive breast cancer treated at Memorial Sloan Kettering Cancer Center from January 1998 to December 2010. A total of 11,596 tumors were classifiable into clinical surrogates for molecular subtype by immunohistochemical analysis: hormone receptor (HR)+/HER2+, HR+/HER2?, HR?/HER2+, and TN (HR?/HER2?). Multivariable logistic regression analysis (MVA) was used to determine associations between clinicopathologic variables and subtype.

Results

There were differences in age, tumor size, LVI, grade, and nodal involvement among groups. On MVA controlling for size, grade, and age, ER, PR, and HER2 status were significantly associated with LVI (p < 0.0001). Relative to TN tumors, HR+/HER2?, HR+/HER2+, and HR?/HER2+ tumors had higher odds of demonstrating LVI of 1.8 (odds ratio 1.8; 95 % confidence interval 1.6–2.1), 2.5 (2.5; 2.0–3.0), and 1.7 (1.7; 1.4–2.1), respectively. On MVA adjusting for size, grade, LVI, and age, TN tumors had the lowest odds of having any or high-volume nodal involvement (≥4 nodes, p < 0.0001).

Conclusions

LVI and nodal metastases were least frequent in TN cancers compared with other subtypes, despite the uniformly worse prognosis and increased LR rate in TN tumors. This suggests TN cancers spread via lymphatics less frequently than other subtypes and ALND may be avoided in TN patients meeting Z0011 eligibility criteria.     

Nodal Pathologic Complete Response Rates in Luminal Breast Cancer Vary by Genomic Risk

Background

Although an advantage of neoadjuvant chemotherapy (NAC) is eradication of axillary disease, nodal pCR rates are much lower for ER+/HER2? breast cancer than other subtypes. We sought to evaluate the association of genomic risk with nodal pCR in ER+/HER2? disease.

Methods

Patients with ER+/HER2? clinically-node-positive (cT0-cT4d/cN1-cN3/cM0) breast cancer treated with NAC and surgery 2010–2018 in the National Cancer Database were identified. Low genomic risk was classified as Oncotype Dx Recurrence Score (RS) 0–25, or Mammaprint 70-gene or RS coded as “Low.” High genomic risk included RS >25, or 70-gene or RS coded as “High.” Nodal pCR was compared between patients with high versus low genomic risk by using chi-square tests and multivariable logistic regression.

Results

Of 15,698 patients, genomic risk was available for 692 of 15,698 (4.4%). High genomic risk was similar between patients aged <50 years versus 50+ (50.8% vs. 57.3%, p = 0.10). Nodal pCR was higher in high genomic risk (25.0%) than low genomic risk (10.4%, p < 0.001). This difference was observed both for patients aged <50 years (29.9% vs. 9.8%) and aged ≥50 years (22.7% vs. 10.8%). On multivariable analysis adjusted for potential confounding variables, including age, grade, and PR status, genomic risk was independently associated with decreased odds of residual nodal disease (odds ratio 0.49, p = 0.002).

Conclusions

For patients with node-positive ER+/HER2? breast cancer treated with NAC, nodal pCR was highest in patients aged <50 years with high genomic risk tumors. In contrast, nodal pCR rates were low in patients with low genomic risk tumors, regardless of age. This information may help when counseling patients regarding axillary management.

     

Isolated pachymeningeal metastasis from breast cancer: Clinical features and prognostic factors

PurposeTo evaluate the clinical features and prognoses of patients with isolated pachymeningeal metastasis (IPM) from breast cancer.MethodsWe reviewed the medical records of all patients with metastatic breast cancer (MBC) treated from January 2009 to August 2016. Eligibility criteria included diagnosis of pachymeningeal metastasis based on brain magnetic resonance imaging and histologic diagnosis of primary breast cancer. We excluded patients with concomitant parenchymal or leptomeningeal metastases.ResultsThirty-eight patients who matched our inclusion criteria were included in this study. The incidence of IPM in breast cancer was 1.5% of all patients with MBC. The molecular subtype distribution was: triple negative, 29.0%; ER+/HER2−, 44.7%; ER+/HER2+, 18.4%; and ER−/HER2+, 7.9%. All isolated pachymeningeal involvement resulted from the direct extension of skull metastases. The median time to IPM from systemic metastasis was 28.6 (95% CI: 23.6–33.6) months. The median time to IPM from skull metastasis was 5.2 (95% CI: 0–10.9) months. The median overall survival (OS) from IPM was 4.0 (95% CI: 2.5–5.5) months. In patients who received chemotherapy the OS was longer than for those who received radiotherapy or supportive care only [median OS 8.9 (95% CI: 0.0–18.4), 2.8 (95% CI: 0.5–5.0), and 0.8 (95% CI: 0.6–1.1) months, respectively (p = 0.006)]. Multivariate analysis revealed that good performance status and chemotherapy were associated with better survival outcomes.ConclusionStratified evaluation is required for patients with skull metastasis from breast cancer, as pachymeningeal involvement can develop and be associated with unsuspected outcomes.