Competing risks of death in NCIC CTG MA.27 adjuvant exemestane versus anastrozole.

564 Background: Our group previously examined if baseline patient/tumor characteristics, or prior treatment affected cause of death in MA.17, a placebo controlled extended adjuvant trial of the aromatase inhibitor (AI) letrozole. We now examine factor effects on all cause mortality in MA.27. Methods: MA.27 was an adjuvant phase III superiority trial of 5 yrs of exemestane vs anastrozole, in ER+ postmenopausal breast cancer accrued between 2003 and 2008; event free survival was similar. We examined by intention-to-treat, the multivariate time-to-breast cancer-specific (BrCa), cardiovascular (Cardio), and other causes (OT) of death with log-normal survival analysis adjusted by treatment and stratification factors (lymph node status, adjuvant chemotherapy, celecoxib, aspirin, and trastuzumab). We tested whether factors were associated with 1) all cause mortality, and if so, 2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. Results: 7,576 women (median age 64.1 years; 5417 (71.5%) <70 yrs and 2159 (28.5%) >70 yrs) were enrolled and followed for a median of 4.1 yrs. The 432 deaths comprised: 187 (43.3%) BrCa, 66 (15.3%) Cardiovascular, and 179 (41.4%) OT MA.27 therapy was not associated with mortality (p=0.84). Five baseline factors were differentially associated with cause of death. Older age was associated with greater BrCa (p=0.03), Cardio (p<0.001), and OT (p<0.001) mortality. Pre-existing cardiovascular history led to worse Cardio mortality (p<0.001). Worse ECOG performance status led to worse OT death (p<0.001). T1 tumors were associated with less BrCa mortality (p<0.001). PgR+ tumors were also associated with less BrCa mortality (p<0.001). There were fewer BrCa deaths with Node –ve disease (p<0.001), ER+ tumors (p=0.001) and without adjuvant chemotherapy (p=0.005); there was worse Cardio mortality (p=0.01) with receipt of trastuzumab; worse OT (p=0.03) for non-whites, and without adjuvant radiotherapy (p=0.003). Conclusions: 56.7% of deaths in MA.27 patients were non-breast cancer related. We showed baseline patient and tumor characteristics, and prior treatment differentially affected cause of death. Clinical trial information: NCT00066573.

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ALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early-stage triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps598 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS598-TPS598

Author(s):

Heather L. McArthur ◽

Michail Ignatiadis ◽

Sebastian Guillaume ◽

Andrew Bailey ◽

Jorge Luis Martinez ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

Disease Free Survival ◽

Phase Iii ◽

Lymph Node Status ◽

Phase 3 ◽

Metastatic Setting

TPS598 Background: Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer and promising clinical activity has been reported with the anti–PD-L1 antibody, atezolizumab, in Phase 1/1b metastatic TNBC trials. Furthermore, the randomized phase 3 IMpassion130 study demonstrated enhanced anti-tumor activity when atezolizumab was co-administered with chemotherapy in the first line metastatic setting, with benefit mainly observed in PD-L1+ cohort. ALEXANDRA/IMpassion030 will evaluate the efficacy and safety of atezolizumab in combination with standard anthracycline/taxane adjuvant chemotherapy in early TNBC patients. Methods: ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard chemotherapy versus chemotherapy alone in early TNBC. In total, 2300 patients with operable stage II or III TNBC, confirmed by central pathology review, will be randomized. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant treatment will consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary end-point is invasive disease-free survival (iDFS) and secondary end-points include iDFS by PD-L1 and lymph node status, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first patient was enrolled on August 2nd 2018, and approximately 430 sites are expected to be opened globally in 30 countries. Clinical trial information: NCT03498716.

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N-SAS BC06: A phase III study of adjuvant endocrine therapy with or without chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole (LET): The New Primary Endocrine-Therapy Origination Study (NEOS).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps654 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS654-TPS654

Author(s):

Hiroji Iwata ◽

Shoichiro Ohtani ◽

Tomomi Fujisawa ◽

Naruto Taira ◽

Norikazu Masuda ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Endocrine Therapy ◽

Response Rate ◽

Postmenopausal Breast Cancer ◽

Phase Iii ◽

Breast Cancer Patients ◽

Er Positive ◽

Phase Iii Study

TPS654 Background: It is uncertain whether adjuvant chemotherapy is required in the treatment of postmenopausal women with hormone-responsive and intermediate risk breast cancer. The TAILORx and MINDACT trials are ongoing and utilize gene expression profiling in order to answer this question. We have initiated a new study to address this matter by using response to initial neoadjuvant endocrine therapy. The primary aim of this phase III study is to evaluate the necessity of using adjuvant chemotherapy for the treatment of postmenopausal breast cancer patients with node-negative, ER-positive and HER2-negative tumors who responded to neoadjuvant LET. Methods: Inclusion criteria are T1c-T2N0M0, ER-positive by IHC (<10%), HER2-negative, postmenopausal women under 75 years old and written informed consent. Lymph node positive patients as assessed by SLNB are excluded. Neoadjuvant LET is administered for 24-28 weeks before surgery. CR, PR or SD patients are then randomized into two arms receiving either chemotherapy plus LET for 4.5-5 years or LET alone for 4.5-5 years after surgery. If the primary tumor response is defined as PD before surgery, the treatment will be changed at the investigator's discretion (surgery, chemotherapy or other endocrine therapy, but these patients will be followed up). The primary endpoint is disease-free survival (DFS), and secondary endpoints are overall survival (OS), response rate of LET, pathological response, breast conserving surgery rate, DFS/OS by response rate of LET, safety, QOL and cost-effectiveness. This study utilizes a randomized selection design. The objective of this design is to select the arm with the better outcome. We also conduct an additional translational research and central pathological review of ER, PgR, HER2, and Ki67.Patient recruitment commenced in May 2008 and 803 patients were enrolled at the end of 2012. A total of 850 patients will be enrolled at the end of May 2013. This study is supported by Public Health Research Foundation. Clinical trial information: UMIN000001090.

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Serum 1-OH vitamin D (D) and prognosis of postmenopausal breast cancer (BC) patients: NCIC-CTG MA14 trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.534 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 534-534 ◽

Cited By ~ 1

Author(s):

E. Piura ◽

J. W. Chapman ◽

A. Lipton ◽

L. Zhu ◽

K. Leitzel ◽

...

Keyword(s):

Breast Cancer ◽

Postmenopausal Breast Cancer ◽

Phase Iii ◽

Lymph Node Status ◽

Bone Resorption Marker ◽

Type I ◽

Axillary Lymph ◽

Blood Draw ◽

Baseline Serum ◽

Free Survival

534 Background: In vitro, D has demonstrated regulatory functions in breast cancer cells and the bone microenvironment. Higher serum D levels were associated in some prior studies with favorable BC prognosis. We previously found that the baseline serum bone resorption marker, beta C-terminal telopeptides of type I collagen (B-CTx), was associated with bone-only first relapse, and that higher levels of insulin secretion as estimated by c-peptide level was associated with reduced event-free survival (EFS). We hypothesized that baseline serum D might be associated with relapse of breast cancer in bone and/or other metastatic sites. Methods: Baseline D was determined for the phase III MA.14 trial of adjuvant tamoxifen (20 mg/day oral for 5 years) ± octreotide (90 mg/month depot injection for 2 years). Stratification was by adjuvant chemotherapy, axillary lymph node status, and hormone receptor status. EFS, time from randomization to recurrence, second malignancy, or death due to any cause, was the primary endpoint. Recurrence-free survival (RFS), time from randomization to recurrence of the primary disease alone, was a secondary endpoint. For both endpoints, step-wise forward multivariate Cox regression adjusted for stratification factors was used to examine the association of D and outcome; a factor was added if p < 0.05. Results: Baseline D levels were available for 607 (91%) patients. As expected, D levels for a population far from the equator varied with month of blood draw (p = 0.007), which gives confidence in assay performance. Continuous D was not associated with RFS of any relapse (p = 0.57), bone only relapse (p = 0.19), bone + other site of relapse (p = 0.73), or all bone relapse types (p = 0.66). D was not associated with EFS (0.43), even when adjusted by season (p = 0.64), level deficiency/insufficiency vs sufficiency/toxicity (p = 0.69), age (p = 0.54), and BMI (p = 0.32). As well, interactions between D and season, age, and BMI were non-significant (respectively, p = 0.90, 0.84, 0.23). Conclusions: D was not associated with EFS or RFS in postmenopausal breast cancer patients in this well controlled hormonal therapy study, a result consistent with some, but not all, studies of this issue. No significant financial relationships to disclose.

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Aromatase inhibitors in breast cancer.

Endocrine Related Cancer ◽

10.1677/erc.0.0110179 ◽

2004 ◽

Vol 11 (2) ◽

pp. 179-189 ◽

Cited By ~ 62

Author(s):

P E L√∏nning

Keyword(s):

Breast Cancer ◽

Aromatase Inhibitors ◽

Cancer Biology ◽

Postmenopausal Breast Cancer ◽

Phase Iii ◽

Cross Resistance ◽

Consistent Difference ◽

Clinical Effects ◽

Endocrine Regulation

The development of aromatase inhibitors for breast cancer therapy is a result of successful translational research exploring the biochemical effects of different compounds in vivo. Studies assessing plasma oestrogen levels as well as in vivo aromatase inhibition have revealed a consistent difference with respect to biochemical efficacy between the third generation compounds (anastrozole, letrozole and exemestane) and the previous, first and second generation drugs, corresponding to the improved clinical effects of these compounds as outlined in large phase III studies. Thus, endocrine evaluation has been found to be a valid surrogate parameter for clinical efficacy. Moreover, the results from these studies have added important biological information to our understanding of endocrine regulation of breast cancer. Based on the clinical results so far, aromatase inhibitors are believed to play a key role in future adjuvant therapy of postmenopausal breast cancer patients and potentially also for breast cancer prevention. Interesting findings such as the lack of cross-resistance between steroidal and non-steroidal compounds should be further explored, as this may add additional information to our understanding of breast cancer biology.

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Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2011.36.7045 ◽

2011 ◽

Vol 29 (34) ◽

pp. 4491-4497 ◽

Cited By ~ 178

Author(s):

Edith A. Perez ◽

Vera J. Suman ◽

Nancy E. Davidson ◽

Julie R. Gralow ◽

Peter A. Kaufman ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Growth Factor Receptor ◽

Disease Free Survival ◽

Standard Of Care ◽

Phase Iii ◽

P Value ◽

Sequential Administration ◽

Taxane Chemotherapy

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

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Ixabepilone plus capecitabine in metastatic breast cancer patients with reduced performance status previously treated with anthracyclines and taxanes: a pooled analysis by performance status of efficacy and safety data from 2 phase III studies

Breast Cancer Research and Treatment ◽

10.1007/s10549-010-1251-y ◽

2010 ◽

Vol 125 (3) ◽

pp. 755-765 ◽

Cited By ~ 15

Author(s):

Henri Roché ◽

Pierfranco Conte ◽

Edith A. Perez ◽

Joseph A. Sparano ◽

Binghe Xu ◽

...

Keyword(s):

Breast Cancer ◽

Performance Status ◽

Safety Data ◽

Metastatic Breast ◽

Pooled Analysis ◽

Phase Iii ◽

Efficacy And Safety ◽

Breast Cancer Patients ◽

Previously Treated ◽

Phase Iii Studies

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Metástasis duodenal de cáncer de mama. Presentación atípica y resolución quirúrgica no habitual

Acta gastroenterológica latinoamericana ◽

10.52787/vdru8702 ◽

2020 ◽

Vol 50 (2) ◽

Author(s):

Roberto Muñoz Jaramillo ◽

Sonia Ojeda ◽

Tomás Fumo ◽

Lucio Uranga ◽

Oscar Zerbo ◽

...

Keyword(s):

Breast Cancer ◽

Gastrointestinal Tract ◽

Adjuvant Chemotherapy ◽

Cause Of Death ◽

Malignant Tumor ◽

Cáncer De Mama ◽

History Of ◽

Metastatic Involvement

Breast cancer is the most frequent malignant tumor and the leading cause of death worldwide. The most frequent sites of metastatic involvement are the bone, liver and lung, and less than 1% compromise the gastrointestinal tract. The case of a patient with a history of breast cancer treated with chemotherapy and subsequent duodenal relapse is presented below. A cephalic duodenopancreatectomy (CDP) and adjuvant chemotherapy were performed with favorable evolution.

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