Systemic Treatment for Brain Metastasis and Leptomeningeal Disease in Breast Cancer Patients.

PURPOSE OF REVIEW: Breast cancer with brain metastasis (BCBM) and leptomeningeal disease (LMD) are important clinical problems. Traditionally, patients with metastases to the brain and meninges were excluded from clinical trials; hence, robust, evidence-based treatment recommendations are lacking. In this review, we outline the systemic treatment options and ongoing clinical trials. RECENT FINDINGS: Several recent studies have added to the systemic treatment options available. Antibody-drug conjugates have changed the therapeutic landscape. Combination treatment modalities that target multiple mechanisms including disruption of the blood brain barrier are increasingly being studied. Breast cancer with brain metastases and LMD is a heterogenous disease. While the prognosis remains grim, with more systemic treatment options, patients with BCBM are now living longer. Many ongoing clinical trials hold promise to further improve outcomes.

Association of HSD3B1 Genotype and Clinical Outcomes in Postmenopausal Estrogen-Receptor-Positive Breast Cancer.

BACKGROUND: Homozygous inheritance of a single-nucleotide polymorphism (1245A > C) in HSD3B1 results in an adrenal permissive phenotype of increased adrenal steroid precursor conversion to potent androgens. This is associated with poor outcomes in prostate cancer. We hypothesized that inheritance of the HSD3B1 adrenal permissive genotype would similarly negatively impact breast cancer outcomes. PATIENTS AND METHODS: Germline HSD3B1 was sequenced in 644 postmenopausal women diagnosed between 2004 and 2015 with stage I-III estrogen receptor-positive (ER+), HER2/neu-negative (HER2-) breast cancer enrolled in a population-based study in western Washington. Primary endpoint was distant metastatic recurrence according to genotype. Secondary endpoint was breast cancer-specific survival. Hazard ratios (HR) were calculated using cause-specific Cox regression accounting for competing risks. RESULTS: Adrenal restrictive genotype (homozygous wild type) was most prevalent (47%), followed by heterozygous (44%) and adrenal permissive (9%). There were no significant differences comparing demographic, tumor, or treatment characteristics apart from higher frequency of adrenal permissive genotype among non-Hispanic white participants (p = 0.04). After accounting for competing risks, the cumulative incidence of distant metastatic recurrence (15 events) was significantly higher among participants with adrenal permissive compared with the adrenal restrictive genotype (HR 4.9, 95% CI 1.32-18.4, p = 0.02). The adrenal permissive genotype was also predictive of breast cancer-specific mortality (HR 3.5, 95% CI 1.27-9.59, p = 0.02). CONCLUSIONS: Inheritance of the HSD3B1 adrenal permissive genotype is associated with increased incidence of distant metastasis and higher cause-specific mortality in postmenopausal ER+/HER2- breast cancer. Further research is necessary to understand the effect of excess adrenal androgen metabolism in promoting breast cancer growth and progression.

Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microchimerism.

HLA class II genes provide the strongest genetic contribution to rheumatoid arthritis (RA). HLA-DRB1 alleles encoding the sequence DERAA are RA-protective. Paradoxically, RA risk is increased in women with DERAA+ children born prior to onset. We developed a sensitive qPCR assay specific for DERAA, and found 53% of DERAA-/- women with RA had microchimerism (Mc; pregnancy-derived allogeneic cells) carrying DERAA (DERAA-Mc) vs. 6% of healthy women. DERAA-Mc quantities correlated with an RA-risk genetic background including DERAA-binding HLA-DQ alleles, early RA onset, and aspects of RA severity. CD4+ T cells showed stronger response against DERAA+ vs. DERAA- allogeneic cell lines in vitro, in line with an immunogenic role of allogeneic DERAA. Results indicate a model where DERAA-Mc activates DERAA-directed T cells that are naturally present in DERAA-/- individuals and can have cross-reactivity against joint antigens. Moreover, we provide an explanation for the enigmatic observation that the same HLA sequence differentially affects RA risk through Mendelian inheritance vs. microchimeric cell acquisition.

Cancer and Pregnancy: National Trends.

OBJECTIVE: Cancer and pregnancy are likely increasing; however, updated estimates are needed to optimally address the unique needs of this patient population. The study aims to estimate the prevalence of cancer and cancer survivorship at delivery, to test the change in odds of cancer and cancer survivorship at delivery over the 10-year period, and to compare medical conditions, serious events, and obstetric complications between pregnancies with and without cancer at delivery. STUDY DESIGN: We conducted a retrospective analysis of the National Inpatient Sample (NIS), the largest all-payer inpatient health database in the United States. We identified delivery admissions from 2004 to 2013 with a concurrent diagnosis of cancer using International Classification of Disease, ninth revision (ICD-9) codes. Multivariable logistic regression was used to test the change in prevalence of concurrent cancer, cancer survivorship, and pregnancy and to compare outcomes between deliveries with and without cancer. All analyses were adjusted for NIS-provided population weights and strata. RESULTS: During the study period, the NIS represented a national estimate of 40,855,208 deliveries. The odds of cancer increased from 3.41/10,000 deliveries in 2004 to 4.33/10,000 in 2013. This trend was statistically significant, including after adjustment for maternal age (adjusted odds ratio [aOR] = 1.03 [95% confidence interval (CI): 1.01-1.04]). Cancer survivorship at delivery increased significantly (aOR = 1.07 [95% CI: 1.06-1.08]). Women with cancer more often experienced one or more of the following: death, ventilation, cardiac arrest, sepsis, or acute respiratory or renal failure during delivery (aOR for composite outcome 10.7 [95% CI: 6.6-17.2]), even after adjustment in a multivariable logistic regression model. CONCLUSION: The odds of cancer and cancer survivorship at delivery increased from 2004 to 2013, independent of maternal age. Women with cancer were more likely to experience medical or obstetric complications during their delivery compared with women without cancer. These findings highlight the importance of obstetric and oncologic clinical and research collaboration to improve patient care. KEY POINTS: · The odds of cancer at delivery increased.. · Women with cancer may have delivery complications.. · Cancer survivorship at delivery increased..

Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer.

BACKGROUND: Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician's choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. METHODS: We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. FINDINGS: We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. INTERPRETATION: Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial).

PURPOSE: Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). METHODS: Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6-12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. RESULTS: Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23-53) among 18 who had received TH and 46 (range 34-54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045). CONCLUSION: Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.

Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects.

Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1-7 and idarubicin (12 mg/m2) on days 1-3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high-risk and seven (44%) had standard-risk cytogenetics. Ten episodes of CRS were observed. No cases of GVHD or treatment-related mortality were reported. Event-free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high-risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor-specific T cell clones.

Obstetric Outcomes in Young Women with Breast Cancer: Prior, Postpartum, and Subsequent Pregnancies.

OBJECTIVE: This study aimed to describe obstetric outcomes in a large cohort of young women with breast cancer, considering the chronological relationship of pregnancies with breast cancer diagnosis. STUDY DESIGN: From a population-based cohort study of young women with breast cancer from 2004 to 2010, we conducted secondary interviews to obtain detailed obstetric histories. Pregnancies were categorized based on timing of breast cancer diagnosis: prior, postpartum, and subsequent pregnancies after breast cancer diagnosis. A generalized estimated equation model was used to account for correlated data. RESULTS: In this cohort (n = 366), median age at breast cancer diagnosis was 40.1 years, and 84.7% were Caucasian. Tumor type was notable for 25.1% triple negative, and 56.1% had Stage I disease. There were 922 prior pregnancies, 21 with postpartum diagnosis of breast cancer, and 24 pregnancies subsequent to breast cancer diagnosis. Non-live birth outcomes occurred significantly more often in the postpartum group (p-value: 0.001) compared with the other groups, which had higher live birth rates, after adjustment for maternal age, parity, body mass index, and race. CONCLUSION: Overall, pregnancy outcomes before and after breast cancer diagnosis are reassuring.

Diffusion-weighted MRI characteristics associated with prognostic pathological factors and recurrence risk in invasive ER+/HER2- breast cancers.

BACKGROUND: Hormone receptor-positive breast cancer is the most common subtype; better tools to identify which patients in this group would derive clear benefit from chemotherapy are needed. PURPOSE: To evaluate the prognostic potential of diffusion-weighted MRI (DWI) by investigating associations with pathologic biomarkers and a genomic assay for 10-year recurrence risk. STUDY TYPE: Retrospective. SUBJECTS: In all, 107 consecutive patients (from 2/2010 to 1/2013) with estrogen receptor (ER)-positive/HER2neu-negative invasive breast cancer who had the 21-gene recurrence score (RS) test (Oncotype DX, Genomic Health). FIELD STRENGTH/SEQUENCE: Each subject underwent presurgical 3T breast MRI, which included DWI (b = 0, 800 s/mm2 ). ASSESSMENT: Apparent diffusion coefficient (ADC) and contrast-to-noise ratio (CNR) were measured for each lesion by a fifth year radiology resident. Pathological markers (Nottingham histologic grade, Ki-67, RS) were determined from pathology reports. Medical records were reviewed to assess recurrence-free survival. STATISTICAL TESTS: RS was stratified into low (<18), moderate (18-30), and high (>30)-risk groups. Associations of DWI characteristics with pathologic biomarkers were evaluated by binary or ordinal logistic regression, as appropriate, with adjustment for multiple comparisons. Post-hoc comparisons between specific groups were also performed. RESULTS: ADCmean (odds ratio [OR] = 0.61 per 1 standard deviation [SD] increase, adj. P = 0.044) and CNR (OR = 1.76 per 1-SD increase, adj. P = 0.026) were significantly associated with increasing tumor grade. DWI CNR was also significantly associated with a high (Ki-67 ≥14%) proliferation rate (OR = 2.55 per 1-SD increase, adj. P = 0.026). While there were no statistically significant linear associations in ADC (adj. P = 0.80-0.85) and CNR (adj. P = 0.56) across all three RS groups by ordinal logistic regression, post-hoc analyses suggested that high RS lesions exhibited lower ADCmean (P = 0.037) and ADCmax (P = 0.004) values and higher CNR (P = 0.008) compared to lesions with a low or moderate RS. DATA CONCLUSION: DWI characteristics correlated with tumor grade, proliferation index, and RS, and may potentially help to identify those with highest recurrence risk and most potential benefit from chemotherapy. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2017.

Adjuvant continuous metronomic adriamycin + cyclophosphamide followed by weekly nab-paclitaxel for high-risk early-stage breast cancer.

Many studies have sought to optimize the dosing schedule of adjuvant chemotherapy in early-stage breast cancer. Here, we assessed the use of continuous metronomic weekly doxorubicin plus daily oral cyclophosphamide (AC) with continuous G-CSF growth factor support for 12 weeks followed by weekly nab-paclitaxel (nP) for 12 weeks. A nonrandomized phase II clinical trial was designed to assess (1) DFS at 2 years, (2) dose delivered, (3) use of nP in the adjuvant setting, and (4) toxicities. The dosing of A was 24 mg/m2 IV weekly and C was 60 mg/m2 oral daily (with scheduled filgrastim 5mcg/kg 6 days/week); nP, 100 mg/m2 IV weekly. For patients with HER2 + disease, trastuzumab was started during the nP portion of therapy and continued for 12 months. Sixty patients enrolled with a median follow-up of 6 years. Node-positive disease was present in 58% of patients. Receptor categories included hormone receptor positive/HER2 negative (n = 25; 42%); triple negative (n = 19; 32%); or HER2 positive (n = 16; 27%). DFS at 2 years was 93%. Mean dose delivered was greater than 90% for metronomic AC and 88% for nP. Treatment was well tolerated with a 2% incidence of febrile neutropenia. Continuous metronomic AC followed by nP was well tolerated in our patients with comparable DFS to historical controls.

The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

BACKGROUND: Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. OBJECTIVE: To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. DESIGN: Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). DATA SOURCES: Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. TARGET POPULATION: U.S. women aged 50 to 74 years. TIME HORIZON: 10 and 25 years. PERSPECTIVE: Population. INTERVENTION: Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. OUTCOME MEASURES: Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. RESULTS OF BASE-CASE ANALYSIS: At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. RESULTS OF SENSITIVITY ANALYSIS: Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. LIMITATION: Disease models simplify reality and cannot capture all breast cancer subtypes. CONCLUSION: Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. PRIMARY FUNDING SOURCE: University of Washington and National Cancer Institute.

Statistical Methods for Unusual Count Data: Examples From Studies of Microchimerism.

Natural acquisition of small amounts of foreign cells or DNA, referred to as microchimerism, occurs primarily through maternal-fetal exchange during pregnancy. Microchimerism can persist long-term and has been associated with both beneficial and adverse human health outcomes. Quantitative microchimerism data present challenges for statistical analysis, including a skewed distribution, excess zero values, and occasional large values. Methods for comparing microchimerism levels across groups while controlling for covariates are not well established. We compared statistical models for quantitative microchimerism values, applied to simulated data sets and 2 observed data sets, to make recommendations for analytic practice. Modeling the level of quantitative microchimerism as a rate via Poisson or negative binomial model with the rate of detection defined as a count of microchimerism genome equivalents per total cell equivalents tested utilizes all available data and facilitates a comparison of rates between groups. We found that both the marginalized zero-inflated Poisson model and the negative binomial model can provide unbiased and consistent estimates of the overall association of exposure or study group with microchimerism detection rates. The negative binomial model remains the more accessible of these 2 approaches; thus, we conclude that the negative binomial model may be most appropriate for analyzing quantitative microchimerism data.

The use of stereotactic radiosurgery for brain metastases from breast cancer: who benefits most?

Brain metastases (BM) from primary breast cancer can arise despite use of systemic therapies that provide excellent extracranial disease control. Local modalities for treating BM include surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). We sought to determine the benefits of SRS for management of BM arising from different biologic breast cancer subtypes. We reviewed records of 131 patients who received SRS for breast cancer BM between 2001 and 2013. Survival was estimated by the Kaplan-Meier method. Effects of tumor biology, number and location of lesions, and number of SRS sessions on survival were evaluated by Cox proportional hazards regression. Of the 122 patients with subtypes available, 41 patients (31%) were classified as estrogen receptor positive/HER2 negative (ER(+)HER2(-)); 30 patients (23%), ER(+)HER2(+); 23 patients (18%), ER(-)HER2(+); and 28 patients (21%), ER(-)HER2(-) (or triple negative breast cancer, TNBC). Median age at first SRS was 50 years. Median overall survival for ER(+)HER2(-), ER(+)HER2(+), ER(-)HER2(+), and TNBC was 16, 26, 23, and 7 months, respectively (p < 0.001 for difference between groups). Patients with TNBC had the shortest time to retreatment with WBRT or SRS or death with hazard ratio of 3.12 (p < 0.001) compared to ER(+)HER2(-). In all subtypes other than TNBC, SRS can provide meaningful control of BM even in the setting of multiple lesions and may be worth repeating for new lesions that develop metachronously. For patients with TNBC, prognosis is guarded following SRS, and there is an urgent need to develop more effective treatment strategies.

Adjuvant Endocrine Therapy in Patients with Ductal Carcinoma In Situ: A Population-Based Retrospective Analysis from 2005 to 2012 in the National Cancer Data Base.

BACKGROUND: Adjuvant endocrine therapy (AET) has been shown to reduce the risk of second breast cancer events in women with ductal carcinoma in situ (DCIS). There is no population-level evaluation of AET use in DCIS patients after standardized reporting of estrogen receptor (ER) status in cancer registries in 2004. METHODS: We conducted a retrospective cohort study of women with DCIS in the National Cancer Data Base between 2005 and 2012. Patient, tumor, and treatment characteristics as well as temporal trends associated with receipt of AET were evaluated by generalized linear regression. RESULTS: Among 206,255 DCIS patients, 36.5% received AET. Fewer than half of ER-positive patients (n = 62,146, 46.4%) received AET, with a modest but significant increase over time (43.6% in 2005 to 47.5% in 2012; unadjusted p trend <0.001). AET decreased among ER-negative patients (8.9-6.5%, p trend <0.001) over the same time period. On multivariate analysis, younger (<40 years) and older (≥70 years) women were less likely to receive AET than 50- to 59-year-old women (<40 years: relative risk 0.86, 95% confidence interval 0.82-0.89; ≥70 years: relative risk 0.79, 95% confidence interval 0.77-0.81). ER-positive status conferred a 6.15-fold higher likelihood of receiving AET compared to ER-negative status (95% confidence interval 5.81-6.50). Women who underwent breast-conserving surgery (BCS) with adjuvant radiotherapy were most likely to receive AET. CONCLUSIONS: Receipt of AET is relatively low in the group of women most likely to benefit from its use, namely ER-positive patients who underwent BCS. Significant variation exists with respect to patient, tumor, site, and treatment factors. More tolerable drugs or clearer guideline recommendations may increase use.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT.

PURPOSE: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need. METHODS: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. RESULTS: After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). At 5 years, the recurrence-free interval (RFI) was 98.3% (95% CI, 97.0 to 99.7), the overall survival was 97.8% (95% CI, 96.3 to 99.3), and the breast cancer-specific survival was 99.4% (95% CI, 98.6 to 100). Comparable iDFS was observed with T-DM1 irrespective of tumor size, hormone receptor status, centrally determined HER2 immunohistochemical score, and receipt of T-DM1 for more or less than 6 months. Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%. Among patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes significantly differed according to HER2DX risk score, with better RFI (98.1% v 81.8%, hazard ratio [HR], 0.10, P = .01) and iDFS (96.3% v 81.8%, HR, 0.20, P = .047) among patients with HER2DX low-risk versus high-risk tumors, respectively. CONCLUSION: Adjuvant T-DM1 for 1 year leads to outstanding long-term outcomes for patients with stage I HER2-positive breast cancer. A high HER2DX risk score predicted a higher risk of recurrence in ATEMPT.

Preoperative Systemic Therapy for Breast Cancer.

The indications for preoperative/neoadjuvant systemic therapy in breast cancer have changed over the past few years. In this article, the authors review the current data for use of neoadjuvant therapy in inoperable and operable settings. The evolution of various neoadjuvant regimens used in triple-negative breast cancer, human epidermal growth factor receptor 2 (HER2) overexpressing/gene-amplified (HER2+) tumors, and hormone receptor positive breast cancer is discussed as well as the role of neoadjuvant chemotherapy in tailoring adjuvant treatment.