Therapy For Primary Breast Cancer Research Articles

Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year follow-up.

This study was designed to explore whether zoledronic acid could prevent expected loss of bone mineral density (BMD) in postmenopausal women with pre-existing osteopenia or osteoporosis who were initiating adjuvant letrozole therapy for primary breast cancer. Between June 2006 and July 2007, 60 postmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a BMD T-score ≤-2.0 were enrolled. Participants received letrozole 2.5 mg and vitamin D 400 IU daily, calcium 500 mg twice daily, and zoledronic acid 4 mg every 6 months for a maximum of 5 years or until disease progression. BMD at the lumbar spine and femoral neck was recorded at the start of the study and annually for 5 years. Patients were evaluated for fractures every 6 months for the duration of the trial. After 5 years, mean BMD increased significantly by 11.6% (p = 0.01) at the lumbar spine and by 8.8% (p = 0.01) at combined sites. Femoral neck BMD increased by 4.2%, although this was not significant (p = 0.23). At the end of the trial, BMDs were consistent with osteoporosis in 7 % and osteopenia in 36% of the patients. A total of six fractures were reported after 417 individual assessments. Zoledronic acid appears to prevent further bone loss in postmenopausal breast cancer patients with osteopenia and osteoporosis starting treatment with letrozole. These findings were maintained at 5 years and support concurrent initiation of bisphosphonate and aromatase inhibitor therapy in this high-risk population.

Abstract 3327: Metabolomics: Potential molecular mechanisms of radiotherapy (RT)-related normal tissue toxicities in breast cancer

Abstract Breast cancer is the most frequently diagnosed cancer in women and the second leading cause of cancer death in American women. Clinical guidelines recommend that when breast-conserving surgery is provided as a primary therapy for early-stage breast cancer, RT should follow to improve clinical outcome. Although well tolerated by most patients, even with improved RT technology, breast cancer patients experience moist desquamation as early adverse skin reactions. To elucidate the molecular mechanisms involved in RT-related normal tissure toxicity, global metabolomic profiles were determined in urine samples comparing across paired pre-RT and post-RT samples from 60 breast cancer patients exhibiting low (n = 30) or high (n = 30) skin toxicity in response to RT. The extracted samples were split into equal parts for analysis on the GC/MS and LC/MS platforms. The dataset comprises a total of 478 compounds of known identity. Preliminary data suggest that pre-RT glucose and a variety of derivatives linked to the pentose phosphate pathway, such as ribulose, or the consumption of pyruvate in the mitochondrial tricarboxylic acid cycle, including citrate and succinate, were significantly elevated in the high toxicity group. Multiple metabolites derived from the oxidation of aromatic compounds such as amino acids and dietary polyphenolics - vanillate, 3-hydromandelate, tyramine, 3-methoxy-4-hydroxyphenylglycol, and 2-hydroxyphenylacetate - were elevated in a trending or significant fashion at the pre-RT baseline in the high toxicity relative to the low toxicity group. Pre-RT ascorbate depletion and accumulation of tobacco metabolites were associated with radiation sensitivity. Ascorbate was significantly decreased at baseline in the high toxicity group and its pre-RT levels were negatively correlated with post-RT skin toxicity. Nicotine derivatives were only detected in 12% of the pre- and post-RT samples but their presence seemed to be a risk factor that could predispose smokers to unfavorable outcomes during radiation therapy. Histamine breakdown markers provided an indication of a heightened inflammatory activity in individuals who experienced toxicity as suggested that anti-histamines might be useful to prevent sensitivity. Our preliminary data suggest the potential application of metabolomics in predicting and monitoring RT-related normal tissue toxicities; future larger studies are warranted to confirm out promising findings and identify targeted metabolic pathways for effective intervention. Citation Format: Jennifer J. Hu, Eunkyung Lee, Cristiane Takita, Jean L. Wright, Omar L. Nelson. Metabolomics: Potential molecular mechanisms of radiotherapy (RT)-related normal tissue toxicities in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3327. doi:10.1158/1538-7445.AM2015-3327

Phase III trial of bisphosphonates as adjuvant therapy in primary breast cancer: SWOG/Alliance/ECOG-ACRIN/NCIC Clinical Trials Group/NRG Oncology study S0307.

503 Background: Randomized trials and a recent meta-analysis suggest that adjuvant bisphosphonates can decrease recurrence and death, primarily in a postmenopausal population. SWOG S0307 compares e...

Highly reproducible results of breast cancer biomarkers when analysed in accordance with national guidelines – a Swedish survey with central re-assessment

Background. Biomarkers are crucial for decisions regarding adjuvant therapy in primary breast cancer, and their correct assessment is therefore of the utmost importance.Aims. To investigate the concordance between Swedish pathology departments and a reference laboratory, for routine analysis of oestrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2), alone, and in combination (St Gallen subtypes).Methods. This survey included 27 of the 28 pathology laboratories in Sweden, covering 98% of cases of primary breast cancer surgery in Sweden. Paraffin-embedded tumour blocks (n = 270) were collected and sent to the central reference laboratory, together with the originally stained slides, for re-analysis. The primary evaluations were previously performed according to national Swedish guidelines, without any knowledge of the subsequent central assessment.Results. The agreement for ER, PR, and Ki67 was 99% [kappa value (κ) = 0.95], 95% (κ = 0.85), and 85% (κ = 0.70), respectively. The agreement for HER2 (0/1 + vs. 2+/3+) was 85% (κ = 0.64), but when equivocal tumours were further analysed with in situ hybridisation, only one discrepancy was observed. Discrepancies between results for ER and PR seem to be explained by analytical differences, whereas the interpretation of staining seems to be more critical for Ki67 and HER2 immunohistochemistry. The agreement between the results from the Swedish laboratories and the reference laboratory, based on the St Gallen subtypes, was 88% (κ = 0.81).Conclusions. When applying national guidelines, highly reproducible results were obtained in routine assessment of breast cancer biomarkers, and the results of this study confirm the clinical utility of these markers for decisions regarding the treatment of primary breast cancer.

Abstract P1-02-07: Contrast-enhanced ultrasound for evaluation of therapeutic efficacy of radiofrequency ablation for primary breast cancer

Abstract <Purpose> To evaluate therapeutic efficacy of percutaneous ultrasound (US) guided radiofrequency (RF) ablation therapy for primary breast cancer using contrast-enhanced US. <Methods and Materials> The study was approved by the institutional ethics committee, and written informed consent was obtained. Between January 2012 and April 2014, 25 patients with biopsy-confirmed T1 breast cancer underwent RF ablation therapy in one institution. We examined 25 patients with 25 T1 breast cancers by contrast-enhanced MRI/CT, and contrast-enhanced US before and after RF ablation therapy. US guided RF abltion was performed using a 17-gauge internally cooled electrode (Cool-TipTM, Valleylab, Boulder, CO, USA) under general anesthesia. After injection 0.015mL/kg body weight of Sonazoid®(perflubutane), contrast-enhanced US was performed at a low mechanical index (0.17-0.24). Therapeutic success was defined as a lack of contrast enhancement by contrast-enhanced MRI, US and non-viable cancer tissues by US guided vacuum assisted biopsy (VAB) or core needle biopsy (CNB). <Results> Contrast-enhanced US and MRI four weeks or more after RF ablation therapy showed ablation zones and adequate tumor necrosis in all 25 cancer lesions treated. Contrast-enhanced US made it possible to see that tumor vessels of treated lesions had disappeared after treatment. Contrast enhanced MRI showed a lack of stain with ring-like enhancement of ablation zone and non-viable tissues were seen by VAB and/or CNB in 25 ablation zones. <Conclusion> Contrast-enhanced US using Sonazoid® was useful modalities for evaluating the efficacy of RF ablation therapy in breast cancer lesions. Citation Format: Toshikazu Ito, Jyunji Okayama, Kumiko Uji, Masaaki Izukura. Contrast-enhanced ultrasound for evaluation of therapeutic efficacy of radiofrequency ablation for primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-07.

Response evaluation after primary systemic therapy of Her2 positive breast cancer – an observational cross-sectional study.

AimTo evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring.Methods188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab-containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated.Results10 patients (38.5%) in Group 1 and 8 (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1 (P = 0.043) and Group 2 (P = 0.029). PET/CT evaluated by the breast cancer specific criteria (PET/CT Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens = 77.8%, spec = 100%, PPV = 100%, NPV = 71.4%; Group 2: sens = 87.5%, spec = 62.5%, PPV = 70%, NPV = 83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens = 22.2% spec = 100% PPV = 100% NPV = 41.7%; in Group 2: sens = 37.5%, spec = 87.5%, PPV = 75% NPV = 58.3%) or breast ultrasound (Group 1, sens = 83.3% spec = 25% PPV = 62.5% NPV = 50%; Group 2, sens = 100% spec = 12.5% PPV = 41.6% NPV = 100%).ConclusionThe benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.

TBCRC 008: Early Change in 18F-FDG Uptake on PET Predicts Response to Preoperative Systemic Therapy in Human Epidermal Growth Factor Receptor 2-Negative Primary Operable Breast Cancer

TBCRC 008: Early Change in 18F-FDG Uptake on PET Predicts Response to Preoperative Systemic Therapy in Human Epidermal Growth Factor Receptor 2-Negative Primary Operable Breast Cancer

Information Needs of Older Women Faced with a Choice of Primary Endocrine Therapy or Surgery for Early-Stage Breast Cancer: A Literature Review

Primary endocrine therapy (PET) as an alternative to surgery is widely used in the UK for the treatment of older women with operable breast cancer. For women over 70 it has equivalent overall survival to surgery, although local control rates may be inferior. There are trade-offs to be made in deciding between surgery and PET. There has been little research to investigate the information needs of older women or the involvement in decision making they wish to have when faced with this breast-cancer treatment decision. This review examines the information needs of older women (>65 years) regarding the use of surgery or PET for treating operable primary breast cancer, and identifies their preferred format and media for the presentation of this information. The preference for involvement in treatment decision-making among this group will also be considered. © 2014 Springer Science+Business Media.

The Impact of Weight Change During and After Post-Operative Chemotherapy on Breast Cancer Control in Node-Positive Patients Treated With Trimodality Therapy

Objective: The purpose of this investigation was to determine whether an association exists between post-operative chemotherapy weight change and breast cancer control and survival, specifically within a high-risk population of women with node-positive breast cancer diagnosed and treated in the contemporary setting. Methods: A retrospective investigation with the following eligibility criteria: women who underwent primary surgical therapy for invasive breast cancer, were found to have pathologic evidence of nodal involvement, and were treated with adjuvant chemotherapy and radiation therapy. Demographic, tumor-, and treatment-related data were recorded and analyzed for association with disease control and survival outcomes. The post-operative/pre-chemotherapy weight and BMI served as the baseline comparator for future weight/BMI changes. Results: From January 2004 through December 2008, 52 patients were identified for inclusion. At a median follow-up of 77.2 months (range 19.9–119.4, with 85% followed >5 years), 8 patients experienced disease recurrence and 7 patients had died (3 with recurrent disease). Analysis of factors associated with study endpoints identified absolute weight and BMI change at 1, 3, and 4 years post-chemotherapy completion as significantly inversely associated with overall survival, but not associated with freedom from failure. Additionally, a statistically significant association between number of lymph nodes involved and freedom from failure was identified. Conclusion: This investigation did not detect statistically significant associations between weight or BMI change during chemotherapy and disease control or survival within this high-risk population, while the number of lymph nodes involved was directly related to risk of disease failure. Weight change at intervals following chemotherapy completion demonstrated some association with overall survival.

Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes.

IntroductionThe St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 recognized substantial progress in the pathological characterization of breast cancer subtypes. A useful surrogate definition was developed to distinguish luminal A–like breast cancer from luminal B–like disease based on a combination of estrogen receptor (ER), progesterone receptor (PgR) and Ki-67 status, without a requirement for molecular diagnostics. Differences depend upon the choice of the threshold value for Ki-67 and the requirement for substantial PgR positivity. We aimed to verify the suitability of the new surrogate definitions of luminal subtypes in terms of distant disease control in a large series of patients.MethodsWe studied 9,415 women with a median follow-up of 8.1 years who (1) had ER-positive, human epidermal growth factor receptor 2 (HER2)–negative early breast cancer and (2) had undergone surgery at the European Institute of Oncology between 1994 and 2006. We evaluated distant disease-free survival of patients with “low” (<14%), “intermediate” (14% to 19%) or “high” (≥20%) Ki-67 positivity stratified by PgR expression (negative or low versus high). We calculated the cumulative incidence of distant events, considered competing events and performed multivariable analysis adjusted for pathologic tumor stage, pathologic node stage, tumor grade, peritumoral vascular invasion and menopausal status.ResultsLack of substantial PgR positivity was associated with poorer outcomes only for patients with an intermediate Ki-67 level (P < 0.001). The 4,890 patients (51.9%) with low Ki-67 level (any PgR expression level) or with intermediate Ki-67 level but substantial PgR positivity had comparably good outcomes and thus may represent a most advantageous grouping of those with luminal A–like disease.ConclusionsThe updated pathological definition of intrinsic molecular subtypes may maximize the number of patients classified as having the luminal A–like intrinsic subtype of breast cancer and for whom the use of cytotoxic drugs could mostly be avoided.

SWOG S0307 phase III trial of bisphosphonates as adjuvant therapy in primary breast cancer: Comparison of toxicities and patient-stated preference for oral versus intravenous delivery.

558 Background: Bone metastases are a common site of distant recurrence in breast cancer. Evidence from randomized trials, including a recent meta-analysis, suggests that adjuvant bisphosphonates c...

Complexity of the response evaluation during primary systemic therapy of breast cancer.

e12010 Background: We analyzed the accuracy of different response evaluation score systems in a group of breast cancer patients treated with primary systemic therapy (PST). The score systems tested were based on the metabolical, morphological and proliferation markers of tumor response. Methods: We report on 42 patients in whom staging FDG-PET/CTs were carried out before and after the PST. Maximal SUVs (Standardized Uptake Values) and morphological changes were evaluated in the primary tumor (PT) and axillary lymph node (AL) region. Ki-67 labeling indexes (LI) were measured in the core-biopsies and surgical specimens. Response scoring was performed with the Chevallier and Sataloff (pathological), WHO and RECIST (morphological), EORTC and PERCIST (metabolical) systems and a Ki-67 LI score. Results: The SUVmax and size decreased significantly in the PTs (p<0.001;<0.001) and in the ALs (p<0.001;=0.027). Ki-67 LI decrease was significant (p=0.001). Significant differences were detected between the complete re...

Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus).

Several studies have evaluated the clinical effectiveness of endocrine therapy alone in women aged 70 years or over with operable breast cancer and who are fit for surgery. To systematically review the evidence for the clinical effectiveness of surgery (with or without adjuvant endocrine therapy) in comparison to primary endocrine therapy in the treatment of operable breast cancer in women aged 70 years and over, both in terms of local progression and mortality. We conducted an updated search of the Cochrane Breast Cancer Group's Specialised Register (27th March 2013) and new searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 3), MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and www. gov, using the search terms 'early breast cancer', 'endocrine therapy', 'psychosocial' or 'surgery'. Randomised trials comparing surgery, with or without adjuvant endocrine therapy, to primary endocrine therapy in the management of women aged 70 years or over with early breast cancer and who were fit for surgery. We assessed studies for eligibility and quality, and two review authors independently extracted data from published trials. We derived hazard ratios for time-to-event outcomes, where possible, and used a fixed-effect model for meta-analysis. We extracted toxicity and quality-of-life data, where present. Where outcome data were not available, we contacted trialists and requested unpublished data. We identified seven eligible trials, of which six had published time-to-event data and one was published only in abstract form with no usable data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen. Data, based on an estimated 1081 deaths in 1571 women, did not show a statistically significant difference in favour of either surgery or primary endocrine therapy in respect of overall survival. However, there was a statistically significant difference in terms of progression-free survival, which favoured surgery with (474 participants) or without endocrine therapy (164 participants). The hazard ratios (HRs) for overall survival were: HR 0.98 (95% confidence interval (CI) 0.81 to 1.20, P = 0.85; 3 trials, 495 participants) for surgery alone versus primary endocrine therapy; HR 0.86 (95% CI 0.73 to 1.00, P = 0.06; 3 trials, 1076 participants) for surgery plus endocrine therapy versus primary endocrine therapy. The HRs for progression-free survival were: HR 0.55 (95% CI 0.39 to 0.77, P = 0.0006) for surgery alone versus primary endocrine therapy; HR 0.65 (95% CI 0.53 to 0.81, P = 0.0001) for surgery plus endocrine therapy versus primary endocrine therapy (each comparison based on only one trial). Tamoxifen-related adverse effects included hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion. Surgery-related adverse effects included paraesthesia on the ipsilateral arm and lateral thoracic wall in those who had axillary clearance. One study suggested that those undergoing surgery suffered more psychosocial morbidity at three months post-surgery, although this difference had disappeared by two years. Primary endocrine therapy should only be offered to women with oestrogen receptor (ER)-positive tumours who are unfit for surgery, at increased risk of serious surgical or anaesthetic complications if subjected to surgery, or who refuse surgery. In a cohort of women with significant co-morbid disease and ER-positive tumours it is possible that primary endocrine therapy may be a superior option to surgery. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for an infirm older population with ER-positive tumours.

FDG-PET-CT in the early response evaluation for primary systemic therapy of breast cancer

Abstract Primary systemic therapy (PST) is a standard treatment for patients with locally advanced breast cancer. We report one of our patients to demonstrate the optimal use of FDG-PET-CT in the routine clinical workup during PST, especially when clinicians face contradictory clinical and pathological findings, and to show the advantages of this imaging modality in the decision-making process about the initial treatment choice. By reviewing the literature we would also like to confirm that FDG-PET-CT is highly sensitive in the measurement of the early therapeutic response and the prediction of the complete pathological remission, as early as after the first cycle of chemotherapy is administered.

Bone Health in Patients with Breast Cancer: Recommendations from an Evidence-Based Canadian Guideline

Bone loss is common in patients with breast cancer. Bone modifying agents (BMAs), such as bisphosphonates and denosumab, have been shown to reverse or stabilize bone loss and may be useful in the primary and metastatic settings. The purpose of this review is to provide clear evidence-based strategies for the management of bone loss and its symptoms in breast cancer. A systematic review of clinical trials and meta-analyses published between 1996 and 2012 was conducted of MEDLINE and EMBASE. Reference lists were hand-searched for additional publications. Recommendations were developed based on the best available evidence. Zoledronate, pamidronate, clodronate, and denosumab are recommended for metastatic breast cancer patients; however, no one agent can be recommended over another. Zoledronate or any oral bisphosphonate and denosumab should be considered in primary breast cancer patients who are postmenopausal on aromatase inhibitor therapy and have a high risk of fracture and/or a low bone mineral density and in premenopausal primary breast cancer patients who become amenorrheic after therapy. No one agent can be recommended over another. BMAs are not currently recommended as adjuvant therapy in primary breast cancer for the purpose of improving survival, although a major Early Breast Cancer Cooperative Trialists’ Group meta-analysis is underway which may impact future practice. Adverse events can be managed with appropriate supportive care.

Angiosarcoma after breast-conserving therapy: Long-term disease control and late effects with hyperfractionated accelerated re-irradiation (HART)

Background. Secondary angiosarcoma is a malignant cancer that develops in approximately 1% of patients treated with breast-conserving therapy (BCT) for primary breast cancer. Most treatments for secondary angiosarcoma have been unsuccessful and no consensus has been reached on what is the best therapeutic strategy. We report long-term outcomes of patients with secondary angiosarcoma treated with hyperfractionated and accelerated re-irradiation (HART). Material and methods. We retrospectively reviewed the medical records of, and established direct contact with, 14 consecutive patients with secondary angiosarcoma after BCT with axillary lymph node dissection who were treated at our institution with HART with or without surgery from November 1997 to March 2006. With HART, patients received three radiation therapy treatments each day, with a minimum interfraction interval of four hours, five days a week, at 1 Gy per fraction, to total doses of 45 Gy, 60 Gy, and 75 Gy for areas with a moderate risk for subclinical disease, a high risk for subclinical disease, and gross disease, respectively. The minimum follow-up for these patients was six years. Results. Median survival was 7.0 years (range 0.4–14.7 years), with five- and 10-year overall survival rates of 79% [95% confidence interval (CI), 51–93%] and 63% (95% CI 37–84%), respectively, and five- and 10-year cause-specific survival rates of 79% (95% CI 51–93%) and 71% (95% CI 44–89%), respectively. Toxicity was minimal. Conclusion. Our long-term study provides evidence that patients with secondary angiosarcoma after BCT can frequently be cured. Patients treated with HART have higher overall survival, progression-free survival, and cause-specific survival rates than patients who receive only surgery, conventional radiation therapy, or chemotherapy. HART is well tolerated.

Abstract OT1-1-06: A phase 3, randomized, open-label trial comparing trastuzumab emtansine and trastuzumab as adjuvant therapy for HER2-positive primary breast cancer with residual invasive tumor in the breast or axillary lymph nodes following preoperative therapy (KATHERINE)

Abstract Background: HER2-positive patients (pts) who do not achieve pathologic complete response with preoperative chemotherapy and HER2 directed therapy (PST) are at increased risk of recurrence and mortality despite further anti-HER2-targeted and endocrine treatment. The antibody–drug conjugate trastuzumab emtansine (T-DM1) combines the antitumor activities of trastuzumab (H) with intracellular delivery of the cytotoxic agent DM1 via a stable linker. T-DM1 prolonged progression-free survival (PFS) and overall survival (OS) in a phase 3 study in pts with previously treated HER2-positive metastatic breast cancer (MBC) compared with capecitabine and lapatinib. It also prolonged PFS compared with H and docetaxel in a phase 2 study in pts with previously untreated HER2-positive MBC. Trial design: KATHERINE (NCT01772472) is a phase 3, 2-arm, open-label trial in pts with HER2-positive primary breast cancer (BC) who have received PST, including H, and have residual invasive disease after surgery. Pts are randomly assigned 1:1 to adjuvant T-DM1 3.6 mg/kg IV q3w or H 6 mg/kg IV q3w for 14 cycles. Pts can receive concomitant radiotherapy and/or hormonal therapy if clinically indicated. Eligibility criteria: HER2-positive BC (centrally determined IHC 3+ and/or ISH ratio ≥2); clinical stage T1–4, N0–3, M0 (T1a/bN0 ineligible) prior to PST; ECOG PS 0 or 1; adequate surgical excision; ≥6 cycles of preoperative treatment (≥16 weeks total; ≥9 weeks of H and ≥9 weeks of taxane-based chemotherapy); residual invasive breast or axillary lymph node disease after preoperative therapy; ≤12 weeks from surgery to random assignment. Pts with anthracycline exposure equivalent to doxorubicin &amp;gt;240 mg/m2 or significant cardiopulmonary dysfunction are excluded. Specific aims: The primary efficacy endpoint is invasive disease-free survival (IDFS). Secondary endpoints include disease-free survival, OS, distant recurrence-free interval, quality of life, and pharmacokinetics. Safety assessments include all adverse events, abnormal laboratory values, cardiac events, and LVEF. Statistical methods: The log-rank test (stratified by clinical stage, hormone receptor status, preoperative HER2-directed therapy, and pathologic nodal status after preoperative therapy) will be used to compare IDFS between arms. The hazard ratio (HR) and its 95% confidence interval (CI) will be estimated using Cox proportional hazards model (also stratified). The Kaplan-Meier approach will be used to estimate 3-year IDFS rates and 95% CIs for each arm. The final IDFS analysis, which provides 80% power to detect a HR of 0.75 (a 6.5% improvement in 3-year IDFS from 70% in the control arm to 76.5% in the T-DM1 arm) at a 2-sided alpha level of 5%, will be performed after ∼384 IDFS events have occurred. The final OS analysis will be performed at the end of 10 years of follow-up. Interim analyses of IDFS and OS are planned. Current and target accrual: Enrollment to 342 sites in 28 countries began in April 2013, and target accrual is 1484 pts. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-1-06.

Outcome in patients treated with primary endocrine therapy and neoadjuvant endocrine therapy for breast cancer: A single centre experience

Outcome in patients treated with primary endocrine therapy and neoadjuvant endocrine therapy for breast cancer: A single centre experience

Concordance between Core Needle Biopsy and Surgical Excision Specimens for Tumour Hormone Receptor Profiling According to the 2011 St. Gallen Classification, in Clinical Practice

To focus on and compare the tumor hormone receptor profiles on core needle biopsy (CNB) and subsequent surgical excision specimens in a large clinical series of invasive breast carcinoma patients, with regard to guidelines proposed at the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. A total of 993 consecutive patients who had hormone receptors (HR) assays performed on both CNB and subsequent surgical excision specimens of invasive carcinomas were included (1,110 tumors). Concordant tumor HR profiles between CNB and surgical excision specimens were noted in 1,085 of 1,110 tumors (97.75%). Among 138 tumors considered negative on CNB (both HR assays <1%), 10 cases (7.2%) displayed an HR profile positive on surgical excision specimen. Discrepancies between CNBs and surgical excision specimens are very seldom noted. HR assay evaluation on surgical excision specimens should only be considered in patients when both HR assays are negative on CNBs.

The presence and prognostic impact of apoptotic and nonapoptotic disseminated tumor cells in the bone marrow of primary breast cancer patients after neoadjuvant chemotherapy.

IntroductionNeoadjuvant systemic therapy of primary breast cancer (PBC) patients offers the possibility to monitor treatment response. However, patients might have metastatic relapse despite achieving a pathologic complete response (pCR). This indicates that local response to therapy must not be representative for systemic treatment efficacy. Therefore, the aim of this study was to compare local response with systemic tumor cell dissemination by determining the presence of disseminated tumor cells (DTCs), including apoptotic tumor cells, in the bone marrow (BM) of PBC patients after neoadjuvant chemotherapy (NACT).MethodsDTCs were detected by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology (DTC status). The presence of apoptotic tumor cells was determined by using the M30 antibody (M30 status). This antibody detects a neo-epitope that is expressed only during early apoptosis.ResultsBM aspirates from 400 PBC patients that had completed NACT were eligible for this study. Of these, 167 (42%) patients were DTC positive (DTC status). The M30 status was investigated in 308 patients. Apoptotic (M30-positive) tumor cells were detected in 89 (29%) of these. Whereas the DTC status was not correlated (P = 0.557) to local treatment response (that is, pCR or a clinical complete/partial response), the presence of M30-positive tumor cells was significantly higher in patients that responded to therapy (P = 0.026). Additionally, DTC-positive patients were at an increased risk for disease relapse (hazard ratio, 1.87; 95% CI, 1.11 to 3.15; P = 0.019).ConclusionThe presence of DTC is independent of therapy response of the primary tumor. As patients that are DTC positive after NACT have an unfavorable outcome, they might benefit from additional systemic treatment.