Clinical Significance of HER2-Positive and Triple-Negative Status in Small (≤ 1 cm) Node-Negative Breast Cancer

BackgroundData regarding the clinical significance of HER2⁺ and TN status in patients with small node-negative tumors are limited and conflicting. It remains unclear who, among those with small lesions, might benefit from more aggressive adjuvant therapy.Patients and MethodsWe identified all node-negative breast cancer patients with tumor size ≤ 1 cm diagnosed between January 1, 1995 and December 31, 2008 using our institutional breast service database. Patients were classified according to their receptor status into 3 groups: (1) hormone receptor (HR)-positive (estrogen receptor [ER]- or progesterone receptor [PR]-positive, HER2⁻); (2) HER2⁺ (immunohistochemistry 3⁺ or fluorescence in situ hybridization amplification ≥ 2); and (3) TN (ER⁻, PR⁻, and HER2⁻). RFS was calculated using Kaplan-Meier methods.ResultsAmong 656 patients with tumors ≤ 1 cm, 494 (75%) of the patients were HR⁺, 107 (16%) were HER2⁺, and 55 (9%) were TN. Median age was 59 years (range, 27-92 years). Median follow-up was 3.5 years. The 5-year RFS rates were 98.2%, 97.1%, and 83.5% in patients with HR⁺, HER2⁺, and TN tumors, respectively (P < .001). In multivariate analysis, TN status was associated with worse RFS (hazard ratio, 6.70; 95% confidence interval [CI], 3.02-14.86), and HER2⁺ was not (hazard ratio, 1.64; 95% CI, 0.73-3.69).ConclusionTN, but not HER2⁺ status, was associated with worse RFS in patients with T1abN0 tumors, and adjuvant chemotherapy might be considered in patients with TN breast cancer.     

Incidence and Survival by Human Epidermal Growth Factor Receptor 2 Status in Young Women With Stage I-III Breast Cancer: SEER, 2010-2016

BackgroundYoung premenopausal women with breast cancer often experience more aggressive disease biology and poorer survival than older women. Diagnostic and therapeutic advances, including human epidermal growth factor receptor 2 (HER2)-directed therapy, may lessen treatment burden and improve survival for these young women, but contemporary incidence and survival data by HER2 status are limited.Patients and MethodsWe identified women aged 20-49 years (n = 68,530) diagnosed with stage I-III breast cancer during 2010-2016 from the United States Surveillance, Epidemiology, and End Results 18 registries database. Age-adjusted average annual percent changes in incidence (diagnosis 2010-2016) and 5-year Kaplan-Meier survival curves (diagnosis 2010-2015) were estimated by HER2 and hormone receptor (HR) status and stratified independently by cancer stage and race/ethnicity.ResultsWith increasing age decade, proportions of HER2⁻/HR⁺ cancer increased, whereas proportions of HER2⁺/HR⁺, HER2⁺/HR⁻, and HER2⁻/HR⁻ decreased. The greatest increases in incidence during 2010-2016 were observed for HER2⁺ among women aged 20-49 years and HER2⁻/HR⁻ among women aged 20-29 years. Incidence decreased for HER2⁻/HR⁻ among women aged 40-49 years. Five-year survival was lowest for HER2⁻/HR⁻ status compared to other receptor-based subtypes among women aged 20-49 years. HER2⁺ status was more beneficial for 5-year survival than HR⁺ status among women aged 20-29 years, with the opposite observed among women aged 30-49 years, particularly those aged 40-49 years.ConclusionHER2⁺ breast cancer increased among premenopausal women and was also associated with higher early survival within each HR status. HER2⁻/HR⁻ cancer also increased among women aged 20-29 years and was associated with lower early survival. Our contemporary data provide important insights to help inform preventive and therapeutic strategies for premenopausal women.     

Impact of Subtype on Survival of Young Patients With Stage IV Breast Cancer

BackgroundAlthough younger age is a negative prognostic factor for patients with early stage breast cancer, data regarding the outcomes of young patients with stage IV disease are limited. We evaluated differences in overall survival (OS) according to age and disease subtype among patients with stage IV breast cancer.Patients and MethodsUsing Surveillance, Epidemiology, and End Results (SEER) data, we identified 6,302 patients aged < 60 years with de novo stage IV breast cancer between 2010 and 2014. We examined age-specific OS among hormone receptor (HR)-positive (HR⁺)/human epidermal growth factor receptor 2 (HER2)-negative (HER2⁻), HR⁺/HER2-positive (HER2⁺), HR-negative (HR⁻)/HER2⁺, and triple-negative cases using log-rank tests and Cox proportional hazards models, adjusting for relevant clinical and demographic variables.ResultsCompared with patients aged 40 to 59 years, patients aged < 40 years (n = 944; 15%) had a higher proportion of HER2⁺ cancers and a lower proportion of HR⁺/HER2⁻ disease (P < .001), but a similar proportion of triple-negative disease. Patients aged < 40 years also experienced significantly longer survival, with a median OS of 45 months (vs. 33 months). Further, after stratification by subtype, patients aged < 40 years experienced significantly longer survival, except in the setting of triple-negative disease. These survival differences persisted in adjusted analyses.ConclusionsCompared with those aged 40 to 59 years, patients with de novo metastatic breast cancer aged < 40 years experienced significantly longer survival, except in the setting of triple-negative disease. Distinct treatment-related or biological factors may exist between earlier stage and metastatic breast cancers; further examination of the potential reasons for our findings are warranted.     

A Phase II Open Label Study of Everolimus in Combination With Endocrine Therapy in Resistant Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer

BackgroundTherapies targeting estrogen receptor signaling are standard for patients with hormone receptor (HR)-positive (HR⁺) metastatic breast cancer (MBC). Dysregulation of the phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is associated with treatment resistance. Addition of the mTOR inhibitor, everolimus, to exemestane doubled progression-free survival (PFS) in HR⁺/HER2⁻ MBC patients whose disease had previously progressed during endocrine therapy. In this phase II study, we used everolimus in addition to the most recent endocrine therapy during which a patient's disease progressed, in an attempt to restore and extend the benefit of the antiestrogen therapy in patients with HR⁺/HER2⁻ MBC.Patients and MethodsPatients with HR⁺ MBC who progressed on antiestrogen therapy received everolimus (10 mg orally daily) in combination with the antiestrogen therapy most recently administered. Treatment was administered in 4-week cycles and continued until disease progression or unacceptable toxicity. Blood and archival tumor specimens were collected for VeriStrat (Biodesix, Inc) and Foundation One (Foundation Medicine) assays, respectively. Accrual of 42 evaluable patients allowed detection of improvement in median PFS from 2.8 months (expected with hormonal treatment alone) to 5 months (power 80%, α = 5%).ResultsForty-seven patients were enrolled and treated. After a median follow-up of 22.2 months, median PFS was 6.6 months. Secondary efficacy end points included: overall response rate, 6%; clinical benefit rate, 40%; and median overall survival, 21.1 months. No unexpected toxicity was observed. Efficacy could not be correlated with PI3K/AKT/mTOR alterations or VeriStrat (Biodesix, Inc) prognostic signatures.ConclusionAfter progression during antiestrogen therapy, the addition of everolimus, without changing the hormonal therapy, resulted in a median PFS of 6.6 months, suggesting efficacy in patients with HR⁺/HER2⁻ MBC.     

The Effect of Receptor Status on Mastectomy and Contralateral Prophylactic Mastectomy Rates in Early Stage Invasive Breast Carcinoma

Background

There is an established relationship between hormone receptor (HR; estrogen and/or progesterone receptors) status, HER2 status, and locoregional recurrence. The purpose of this study was to analyze how HR and HER2 receptor status have influenced the surgical management trends among patients with early stage breast cancer.

Development of a Prognostic Factor Index Among Women With HR+/HER2− Metastatic Breast Cancer in a Community Oncology Setting

BackgroundThis study explored the impact of multiple prognostic factors on patient overall survival (OS) and real-world progression-free survival (rwPFS) for patients with hormone receptor-positive (HR⁺)/human epidermal growth factor 2 negative (HER2⁻) metastatic breast cancer (MBC).Materials and MethodsThis retrospective study used electronic health record data of patients in the United States from community oncology practices from January 1, 2008 to April 30, 2017. Eligibility included HR⁺/HER2⁻ MBC diagnosis in 2008 or later and prior systemic therapy for MBC. An index variable was created to assess the effect of multiple clinical prognostic factors collectively, including liver metastases (LM), primary endocrine resistance (PER), negative progesterone receptor (PR⁻) status, and high tumor grade (TG). Patients were grouped based on the number of prognostic factors present at MBC diagnosis: 0, 1, and 2+. Differences in rwPFS and OS from start of first-line therapy were evaluated by the Kaplan-Meier method and multivariable Cox proportional hazards regression.ResultsApproximately 29.1% of the 378 eligible patient sample had 0, 36.0% had 1, and 34.9% had 2+ prognostic factors. For the patients with 1 of the prognostic factors, 24.3% had high TG, 14.7% were LM+, 39.7% had PER, and 21.3% were PR⁻. Univariate and multivariate results showed that rwPFS and OS were significantly (P < .05) shorter in patients with 1 and 2+ prognostic factors compared with patients with 0.ConclusionsThe individual prognostic factors and the prognostic factor index may enable early identification of patients with a less favorable prognosis across the HR⁺/HER2⁻ MBC population and help inform treatment decisions in difficult-to-treat populations.     

Ventriculoperitoneal Shunt for CNS Metastasis in Breast Cancer: Clinical Outcomes Based on Intrinsic Subtype

BackgroundLeptomeningeal metastasis (LM) is associated with a grave prognosis in breast cancer (BC) and can be controlled with a ventriculoperitoneal shunt (VPS). Information regarding LM and VPS based on intrinsic subtype is limited; thus, we investigated the clinical outcomes of BC treated with VPS.Patients and MethodsThe present retrospective study comprised 70 patients diagnosed with LM who received a VPS. The patients were divided into 4 groups based on BC subtype: hormone receptor (HR)⁺/human epidermal growth factor receptor 2 (HER2)⁻, HR⁺/HER2⁺, HR⁻/HER2⁺, and triple negative BC (TNBC).ResultsThe most common indications for VPS were uncontrolled intracranial pressure (57.1%) and uncontrolled headache (55.7%), which improved in 54 (77.1%) of 70 patients after VPS. The median overall survival (OS) after brain or LM and overall survival after VPS were 7.6 and 2.3 months, respectively. Anti-HER2 treatment was a significant prognostic factor for better OS after brain or LM based on multivariate analysis (hazard ratio, 0.15; 95% confidence interval, 0.04-0.57; P = .005), whereas TNBC was correlated with shorter OS after central nervous system metastasis (hazard ratio, 2.82; 95% confidence interval, 1.46-5.48; P = .002).ConclusionsThere were significant differences in clinical outcome based on the intrinsic subtype of patients with BC with LM who received a VPS. Anti-HER2 treatment in patients with HER2⁺ BC was associated with better survival in patients with metastatic BC with VPS insertion compared with those without. Survival of metastatic BC with VPS remained poor, especially in the TNBC subgroup.     

Elucidating Determinants of Survival Disparities Among a Real-world Cohort of Metastatic Breast Cancer Patients: A National Cancer Database Analysis

BackgroundDisparities in breast cancer survival by race/ethnicity and socioeconomic status have been reported. However, it is unclear if these findings are reproducible among subpopulations. This study aimed to assess if socially oriented factors are predictive of overall survival (OS) among patients with hormone receptor-positive (HR⁺), human epidermal growth factor 2-positive (HER2⁺) metastatic breast cancer (MBC).Patients and MethodsWe analyzed patients with MBC included in the National Cancer Database diagnosed with HR⁺ and HER2⁺ disease treated between 2010 and 2015. Multivariate analyses describe the association between non-clinical prognostic factors and OS. A matched analysis, which balanced prognostic factors between whites and African Americans (AA), was also conducted.ResultsOf the 6200 patients analyzed, the majority were 50 years or older, white, and treated with hormonal therapy. Disparities in OS were observed; multivariate analysis revealed diminished survival was associated with low income (< $38K vs. ≥ $63K, hazard ratio [HR], 1.30; P < .001), having government insurance (government vs. private, HR, 1.55; P < .001), living closer to one’s treatment facility (< 4 miles vs. ≥ 18 miles, HR, 1.16; P = .04), and being AA (AA vs. white, HR, 1.20; P = .006). The mortality disparity attributed to race was insignificant in the matched analysis (AA vs. white, HR, 1.13; 95% confidence interval, 0.98-1.30; P = .09).ConclusionsThis study confirms that the known sociodemographic disparities in OS among patients with MBC are similar within the HR⁺/HER2⁺ subpopulation. The discordance of outcomes between matched and unmatched analysis demonstrate that there is a highly vulnerable subgroup of AAs. Further investigation is required to determine if the identified associations are independently causal of poor prognosis.     

The Effect of Adjuvant Treatment in Small Node-negative HER2-positive Breast Cancer: Which Subgroup Will Benefit?

BackgroundWe conducted this study to evaluate whether patients with T1a/b, node-negative (N⁻), human epidermal growth factor receptor 2-positive (HER2⁺) breast cancers benefited from adjuvant therapy, and explored better treatment strategies for these patients.Patients and MethodsPatients with T1a/b, N⁻, HER2⁺ breast cancers during 2000 through 2004 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The Gray test was used to evaluate breast cancer-specific death (BCSD) and non-BCSD. To identify patients more suitable for chemotherapy, subgroup analyses were conducted according to tumor size and estrogen receptor (ER) status, and plots of hazard rate of death (HRD) were drawn to present the changes of BCSD.ResultsA total of 2940 patients with T1a/b, N⁻, HER2⁺ breast cancers were included; more patients in the T1b group received chemotherapy compared with the T1a group (65.18% vs. 29.30%; P < .001). Patients receiving chemotherapy did not benefit from it (5-year incidences of BCSD: 1.00% in the non-chemotherapy group vs. 1.18% in the chemotherapy group; P = .853). Compared with those in the T1a group, patients in the T1b group had similar prognosis (P = .532), whereas ER status was significantly associated with survival (P = .048). HRD had a peak in years 2 to 5, which was more obvious in the ER⁻ group.ConclusionChemotherapy, which is mainly decided by tumor size, fails to render survival benefits for patients with T1a/b, N⁻, HER2⁺ breast cancers. ER status, rather than tumor size, is important for clinicians to make adjuvant treatment decisions. The peak of BCSD occurs 2 to 5 years after diagnosis, and an at least 5-year follow-up is recommended for these patients.     

Clinical Characteristics and Outcomes of Single Versus Double Hormone Receptor–Positive Breast Cancer in 2 Large Databases

PurposeTo identify biologic and outcome differences between double hormone receptor (HR)-positive (dHR⁺, estrogen receptor (ER)⁺/progesterone receptor [PgR⁺]) and single HR-positive (sHR⁺, either ER⁺/PgR⁻ or ER⁻/PgR⁺) breast cancer; and to explore whether hormone therapy (HT) response in HER2-negative breast cancer correlates with HR status.Patients and MethodsThis retrospective study was conducted by using 2 large breast cancer databases: the Surveillance, Epidemiology, and End Results (SEER) database and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) clinical data set. Cox regression analysis was used to estimate overall survival (OS) and breast cancer–specific survival (BCSS) among sHR⁺ and dHR⁺ patients.ResultsIn the SEER database, dHR⁺ patients had significantly longer OS and BCSS than ER⁺/PgR⁻ patients in short-term follow-up (OS: hazard ratio = 0.620; 95% confidence interval [CI], 0.590, 0.652; P < .001; BCSS: hazard ratio = 0.493; 95% CI, 0.462, 0.526; P < .001). Meanwhile, ER⁻/PgR⁺ patients had younger age, larger tumor size, and higher disease grade than dHR⁺ and ER⁺/PgR⁻ patients. In patients who received HT, dHR⁺ patients had a more favorable OS than ER⁺/PgR⁻ patients (hazard ratio = 0.789; 95% CI, 0.635, 0.982; P = .034), and ER⁻/PgR⁺ patients had a worse OS than ER⁺/PgR⁻ patients at 10 years’ follow-up (hazard ratio = 7.991; 95% CI, 1.053, 60.644; P = .044). However, these groups had similar outcomes over longer periods.ConclusionIn HER2-negative breast cancer, sHR⁺ patients are associated with relatively worse characteristics and worse short-term outcomes than dHR⁺ patients. Additionally, the outcome of patients receiving HT may differ according to the HR status. However, further studies are needed to confirm these conclusions.     

Hormone Receptor and Human Epidermal Growth Factor Receptor 2 Detection in Invasive Breast Carcinoma: A Retrospective Study of 12,467 Patients From 19 Chinese Representative Clinical Centers

IntroductionWe evaluated the current status of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detection in invasive breast carcinoma (IBC) in various laboratories across China.Materials and MethodsThe Breast Pathology Study Group of the Chinese Society of Pathologists collected HR and HER2 data from 12,467 IBC cases from 19 representative clinical centers in China. The data from every center were compared with the pooled data from the other centers.ResultsThe assessment of HR status showed that the overall positive estrogen receptor (ER) and progesterone receptor (PR) rates were 71.7% and 63.7% (range, 60.9%-87.9% and 43.9%-84.8%), respectively. The ER results in 3 centers and the PR results in 6 centers were outside the 99.5% confidence interval and were considered to be outliers (P < .0005). Of the 12,467 cases, 62.4% were ER⁺/PR⁺, 9.3% were ER⁺/PR⁻, 1.3% were ER⁻/PR⁺, and 27.0% were ER⁻/PR⁻. The assessment of HER2 status showed that the overall positive rate of HER2 (with a definition of immunohistochemistry [IHC] 3+ or IHC2+/ in situ hybridization-positive) was 24.7% (range, 13.7%-35.7%) in each center. Three centers were outside the 99.5% confidence interval and were considered to be outliers (P < .0005). The proportion of HER2 IHC3+ was 21.1%. The positive rates of HER2 gene amplification in IHC 0/1+, 2+, 3+ cases were 2.0%, 17.6%, and 85.9%, respectively.ConclusionsAs the largest study of HR and HER2 status in Chinese patients with IBC, the data from the present study have indicated that the overall rates of HR and HER2 were comparable to those reported in previous studies. However, the rates varied among the laboratories. Individual centers had not met the target values, and they need to improve the detection.     

Randomized phase II study of primary systemic chemotherapy and trastuzumab for operable HER2 positive breast cancer

BackgroundIn primary systemic therapy in patients with human epidermal growth factor receptor 2 positive (HER2⁺) breast cancer, improvements in pathologic complete response (pCR) rate have been achieved by administering trastuzumab.Patients and MethodsPatients with stage II or IIIA HER2⁺ operable breast cancer were randomly assigned to receive four 3-weekly cycles of FEC (5-fluorouracil 500 mg/m², epirubicin 100 mg/m², cyclophosphamide 500 mg/m²) followed by 4 cycles of 3-weekly trastuzumab (8 mg/kg week 1 and then 6 mg/kg) with either 12 weekly doses of paclitaxel 80 mg/m² (FEC-PH) or 4 cycles of 3-weekly docetaxel 75 mg/m² (FEC-DH).ResultsBetween March 2007 and June 2008, 102 patients were enrolled. Forty-nine patients receiving FEC-PH and 47 receiving FEC-DH were assessable for efficacy and safety. Eighty-four patients completed treatment and underwent surgery. There was no significant difference in the pCR rate between the 2 groups (46.9% [95% CI, 33.7%-60.6%] with FEC-PH vs. 42.6% [95% CI, 29.5%-56.8%] with FEC-DH; P = .67). Analysis by hormone receptor (HR) status showed pCR rates of 54.2% (32/59) in HR^? tumors and 29.7% (11/37) in HR⁺ tumors (P = .02). Among HR^? tumors, the pCR rates were 65.4% and 45.5% in patients treated with FEC-PH and FEC-DH, respectively (P = .13).ConclusionsThere was no significant difference in pCR rate between FEC-PH and FEC-DH. Both regimens achieved higher pCR rates in HR^? than HR⁺ breast cancer, and there was a trend toward higher pCR in HR^? tumors with FEC-PH compared with FEC-DH. Further investigation is warranted to explore the relationship between efficacy and HR status.     

The Role of Immunohistochemistry in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: An Old Tool With an Enduring Prognostic Value

BackgroundTo assess the molecular subtypes determined by hormonal receptors (HR) and human epidermal growth factor receptor 2 (HER2) status and the role of proliferation measured by the Ki-67 marker as predictive and prognostic factors in breast cancer patients treated with neoadjuvant chemotherapy.MethodsA total of 127 breast cancer patients were treated with neoadjuvant chemotherapy every 2 weeks as part of 2 studies. Study A consisted of the administration of Adriamycin (40 mg/m²) on day 1 plus paclitaxel (150 mg/m²) and gemcitabine 2000 mg/m²) on day 2 for 6 cycles (n = 54). Study B consisted of the administration of epirubicin (90 mg/m²), cyclophosphamide (600 mg/m²) on day 1 for 3 cycles, followed by the administration of paclitaxel (150 mg/m²) and gemcitabine 2500 (mg/m²) on day 1 with or without trastuzumab according to HER2 status (n = 73). In study A, patients did not receive trastuzumab regardless of HER2 status. The molecular subtypes of the patients with breast cancer were classified as 49% HR⁺/HER2^?, 17.5% HR⁺/HER2⁺, 13.5% HR^?/HER2⁺, and 20% HR^?/HER2^?.ResultsPathologic complete response (pCR), defined as the absence of invasive cells in the breast and the lymph nodes, was achieved in 35 (28%) patients. The pCR rate was significantly different between the molecular subtypes of breast cancer, with 9% in HR⁺/HER2^?, 23% in HR⁺/HER2⁺, 50% in HR^?/HER2⁺, and 56% in HR^?/HER2^? tumors (P < .001). The pCR rate was significantly higher in tumors that had high Ki-67 (≥20%) expression and were HR^?. HER2⁺ was associated with a higher trend of pCR but did not reach statistical significance. The median follow-up was 81 months (r = 15-150 months). Patients who achieved a pCR had a significantly lower recurrence (P = .01) and higher overall survival (P = .02) compared with those who did not achieve pCR. A multivariate analysis revealed that pCR (hazard ratio 0.24 [95% CI, 0.07-0.7]; P = .019), the molecular subtype (hazard ratio 0.3 [95% CI, 0.1-0.8]; P = .02), and the Ki-67 index (hazard ratio 3.2 [95% CI, 1.4-7.1]; P = .004) were significant independent predictors of disease-free survival. Similar results were obtained for overall survival, in which the pCR rate (hazard ratio 0.119 [95% CI, 0.028-0.5]; P = .004), the molecular subtype (hazard ratio 0.17 [95% CI, 0.03-0.86]; P = .02), and the Ki-67 index (hazard ratio 3.6 [95% CI, 1.3-9.7]; P = .01) also displayed a significant influence on survival.ConclusionsMolecular subtypes and Ki-67 index were independent prognostic factors for disease-free survival and overall survival in breast cancer patients treated with neoadjuvant chemotherapy. A high rate of Ki-67 and HR^? expression were predictors of pCR.     

Clinical Features and Survival of Single Hormone Receptor–Positive Breast Cancer: A Population-Based Study of 531,605 Patients

PurposeTo investigate the prognosis of single hormone receptor–positive (HR⁺) breast cancer (estrogen receptor [ER] positive and progesterone receptor [PR] negative, and ER⁻PR⁺) compared to double HR⁺ (ER⁺PR⁺) and double HR⁻ (ER⁻PR⁻) tumors.MethodsWe included 531,605 cases of invasive breast cancer between 1990 and 2012 from the US Surveillance, Epidemiology, and End Results (SEER) database for study and classified cases into 4 phenotypes according to expression of ER and PR: ER⁺PR⁺, ER⁺PR⁻, ER⁻PR⁺, and ER⁻PR⁻.ResultsOverall, 66,091 ER⁺PR⁻ tumors and 9320 ER⁻PR⁺ tumors were identified. The clinical characteristics of the ER⁺PR⁻ group were similar to those of the double HR⁺ group, while those of the ER⁻PR⁺ and double HR⁻ groups were similar. Overall survival of patients with single HR⁺ tumors was intermediate between that of double HR⁺ and double HR⁻ tumors. However, we observed no differences in disease-specific survival between ER⁻PR⁺ and ER⁻PR⁻ patients. In multivariate analysis, outcomes were similar. Relative to the double HR⁺ patient group, risk of death in the ER⁺PR⁻ group was higher (hazard ratio, 1.422, 95% confidence interval, 1.394-1.452). However, risk of death was comparable between ER⁻PR⁺ and ER⁻PR⁻ patients (hazard ratio, 1.03; 95% confidence interval, 0.98-1.08). Multivariate Cox proportional analysis showed that survival times of patients in the younger age bracket (< 60 years), those positive for human epidermal growth factor receptor 2 (HER2), and patients with tumor stage I-III were longer in the ER⁻PR⁺ group.ConclusionDisease-specific survival of single HR⁺ tumor cases was longer than that of double HR⁻ tumors but poorer than double HR⁺ tumors. However, differences in disease-specific survival were not significant between the ER⁻PR⁺ and ER⁻PR⁻ groups.     

Indications for Postmastectomy Radiation After Neoadjuvant Chemotherapy in ypN0 and ypN1-3 Axillary Node-Positive Women

Introduction

Downstaging with neoadjuvant chemotherapy (NAC) might obscure indications for postmastectomy radiation (PMRT). The degree of downstaging that results in local-regional recurrence (LRR) rates low enough to omit PMRT remains controversial. We examined the rate of LRR in women who received NAC who underwent mastectomy without PMRT.

Does Tumor Size Predict Response to Neoadjuvant Chemotherapy in the Modern Era of Biologically Driven Treatment? A Nationwide Study of US Breast Cancer Patients

BackgroundTumor size has historically been used to stage breast cancer and guide treatment recommendations. The importance of tumor biology in long-term outcomes is increasingly being acknowledged. No large studies have examined the relative roles of tumor size and receptor status on response to neoadjuvant chemotherapy (NAC) in breast cancer.Patients and MethodsThe National Cancer Database was queried for women who underwent NAC and surgery for unilateral clinical stage I to III (cT1-3) invasive breast cancer from 2010 to 2013. Multivariable logistic regression models were used to assess the relation between receptor status, tumor size, and pathologic complete response (pCR) while controlling for other biologic, sociodemographic, diagnosis, and treatment factors.ResultsWe included 38,864 women in this study, most presented with cT2 disease (55%). Patients predominantly had estrogen receptor (ER)/progesterone receptor (PR)-positive (ER/PR⁺) HER2⁻ (45%) or ER/PR⁻ HER2⁻ (28%) disease. Nineteen percent (7432 patients) had a pCR. cT3 (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.59-0.70) but not cT2 cancers (OR, 0.95; 95% CI, 0.89-1.02) were associated with lower pCR rates compared with cT1 disease. HER2⁺ (ER/PR⁺ HER2⁺: OR, 2.94; 95% CI, 2.72-3.18; ER/PR⁻ HER2⁺: OR, 6.45; 95% CI, 5.92-7.02) and ER/PR⁻ HER2⁻ cancers (OR, 3.94; 95% CI, 3.68-4.22) were more likely to experience pCR than those with ER/PR⁺ HER2⁻ cancers. Receptor status was more strongly associated with pCR than tumor size.ConclusionTumor size is independently associated with pCR after NAC after controlling for receptor status, although the effect of receptor status is stronger. These data reinforce the importance of receptor status as well as tumor size, each of which might act as surrogates for tumor biology, in setting expectations for outcomes in patients who undergo NAC.     

Occurrence of breast cancer subtypes in adolescent and young adult women

Introduction

Breast cancers are increasingly recognized as heterogeneous based on expression of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2). Triple-negative tumors (ER^-/PR^-/HER2^-) have been reported to be more common among younger women, but occurrence of the spectrum of breast cancer subtypes in adolescent and young adult (AYA) women aged between 15 and 39 years is otherwise poorly understood.

Methods

Data regarding all 5,605 AYA breast cancers diagnosed in California during the period 2005 to 2009, including ER and PR status (referred to jointly as hormone receptor (HR) status) and HER2 status, was obtained from the population-based California Cancer Registry. Incidence rates were calculated by subtype (triple-negative; HR⁺/HER2^-; HR⁺/HER2⁺; HR^-/HER2⁺), and logistic regression was used to evaluate differences in subtype characteristics by age group.

Results

AYAs had higher proportions of HR⁺/HER2⁺, triple-negative and HR^-/HER2⁺ breast cancer subtypes and higher proportions of patients of non-White race/ethnicity than did older women. AYAs also were more likely to be diagnosed with stage III/IV disease and high-grade tumors than were older women. Rates of HR⁺/HER2^- and triple-negative subtypes in AYAs varied substantially by race/ethnicity.

Conclusions

The distribution of breast cancer subtypes among AYAs varies from that observed in older women, and varies further by race/ethnicity. Observed subtype distributions may explain the poorer breast cancer survival previously observed among AYAs.     

The Prognostic Effect of Changes in Tumor Stage and Nodal Status After Neoadjuvant Chemotherapy in Each Primary Breast Cancer Subtype

Background

Although the prognostic value of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) depends on the intrinsic subtype of breast cancer, it is not clear whether chemosensitivity itself, shown by a decreasing tumor burden after NAC, contributes to improved prognosis in primary breast cancer patients, especially in patients with non-pCR. The aim of this study was to assess the prognostic effect of changes in tumor stage or nodal status after NAC in each primary breast cancer subtype.

HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis

BackgroundHER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT).MethodsA systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins’ I² was used to quantify heterogeneity.ResultsSixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I² = 33%), in HR+ (OR = 3.61, p < 0.001, I² = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I² = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I² = 0%) and in HR + disease (OR = 4.08, p = 0.001, I² = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I² = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I² = 0%).ConclusionsThe HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker.