المؤلفون: Ganz, Patricia A, Bandos, Hanna, Geyer, Charles E, Robidoux, André, Paterson, Alexander HG, Polikoff, Jonathan, Baez-Diaz, Luis, Brufsky, Adam M, Fehrenbacher, Louis, Parsons, Ann W, Ward, Patrick J, Provencher, Louise, Hamm, John T, Stella, Philip J, Carolla, Robert L, Margolese, Richard G, Shibata, Henry R, Perez, Edith A, Wolmark, Norman

المصدر: Breast Cancer Research and Treatment. 192(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Clinical Research, Prevention, Clinical Trials and Supportive Activities, Pediatric, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Chemotherapy, Adjuvant, Cyclophosphamide, Doxorubicin, Epirubicin, Female, Fluorouracil, Humans, Outcome Assessment, Health Care, Quality of Life, Quality of life, Amenorrhea, Cardiac function, Early-stage breast cancer, Adjuvant chemotherapy, Clinical Sciences, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis

الوصف: BackgroundThe NSABP B-36 compared four cycles of doxorubicin and cyclophosphamide (AC) with six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-100) in node-negative early-stage breast cancer. A sub-study within B-36, focusing on symptoms, quality of life (QOL), menstrual history (MH), and cardiac function (CF) was conducted.Patients and methodsPatients completed the QOL questionnaire at baseline, during treatment, and every 6 months through 36 months. FACT-B Trial Outcome Index (TOI), symptom severity, and SF-36 Vitality and Physical Functioning (PF) scales scores were compared between the two groups using a mixed model for repeated measures analysis. MH was collected at baseline and subsequently assessed if menstrual bleeding occurred within 12 months prior to randomization. Post-chemotherapy amenorrhea outcome was examined at 18 months and was defined as lack of menses in the preceding year. Logistic regression was used to test for association of amenorrhea and treatment. CF assessment was done at baseline and 12 months. Correlation analysis was used to address associations between changes in baseline and 12-month PF and concurrent CF changes measured by LVEF.ResultsFEC-100 patients had statistically significantly lower TOI scores during chemotherapy (P = 0.02) and at 6 months (P

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4zj1p1q1Test

المؤلفون: Tutt, Andrew NJ, Garber, Judy E, Kaufman, Bella, Viale, Giuseppe, Fumagalli, Debora, Rastogi, Priya, Gelber, Richard D, de Azambuja, Evandro, Fielding, Anitra, Balmaña, Judith, Domchek, Susan M, Gelmon, Karen A, Hollingsworth, Simon J, Korde, Larissa A, Linderholm, Barbro, Bandos, Hanna, Senkus, Elżbieta, Suga, Jennifer M, Shao, Zhimin, Pippas, Andrew W, Nowecki, Zbigniew, Huzarski, Tomasz, Ganz, Patricia A, Lucas, Peter C, Baker, Nigel, Loibl, Sibylle, McConnell, Robin, Piccart, Martine, Schmutzler, Rita, Steger, Guenther G, Costantino, Joseph P, Arahmani, Amal, Wolmark, Norman, McFadden, Eleanor, Karantza, Vassiliki, Lakhani, Sunil R, Yothers, Greg, Campbell, Christine, Geyer, Charles E

المصدر: New England Journal of Medicine. 384(25)

مصطلحات موضوعية: Digestive Diseases, Breast Cancer, Cancer, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adult, Antineoplastic Agents, Breast Neoplasms, Chemotherapy, Adjuvant, Disease-Free Survival, Double-Blind Method, Female, Genes, BRCA1, Genes, BRCA2, Germ-Line Mutation, Humans, Mastectomy, Middle Aged, Phthalazines, Piperazines, Poly(ADP-ribose) Polymerase Inhibitors, Receptor, ErbB-2, OlympiA Clinical Trial Steering Committee and Investigators, Receptor, erbB-2, Medical and Health Sciences, General & Internal Medicine

الوصف: BackgroundPoly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer.MethodsWe conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival.ResultsA total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9p97543cTest

المؤلفون: Ganz, Patricia A, Cecchini, Reena S, Fehrenbacher, Louis, Geyer, Charles E, Rastogi, Priya, Crown, John P, Thirlwell, Michael P, Ellison, David M, Boileau, Jean-Francois, Flynn, Patrick J, Jeong, Jong-Hyeon, Mamounas, Eleftherios P, Wolmark, Norman

المصدر: npj Breast Cancer. 7(1)

مصطلحات موضوعية: Reproductive Medicine, Biomedical and Clinical Sciences, Contraception/Reproduction, Breast Cancer, Clinical Trials and Supportive Activities, Estrogen, Clinical Research, Cancer, Prevention, Reproductive health and childbirth, Good Health and Well Being, Clinical sciences, Oncology and carcinogenesis, Epidemiology

الوصف: The NRG Oncology/NSABP B-47 menstrual history (MH) study examined trastuzumab effects on menstrual status and associated circulating reproductive hormones. MH was evaluated by questions related to hysterectomy, oophorectomy, and reported menstrual changes. Pre/perimenopausal women were assessed at entry, 3, 6, 12, 18, 24, 30, and 36 months. Consenting women had estradiol and FSH measurement at entry, 3, 6, 12, 18, and 24 months. Logistic regression determined predictors of amenorrhea and hormone levels at 12, 24, and 36 months. Between 2/8/2011 and 2/10/2015, 3270 women with node-positive/high-risk node-negative HER2-low breast cancer were enrolled. There were 1,458 women enrolled in the MH study; 1231 consented to baseline blood samples. Trastuzumab did not contribute to a higher amenorrhea rate. Amenorrhea predictors were consistent with earlier studies; however, to our knowledge, this is the largest prospective study to include serial reproductive hormone measurements to 24 months and clinical amenorrhea reports to 36 months. These data can help to counsel patients regarding premature menopause risk.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/40n22877Test

المؤلفون: Thomas, Alexandra, Reis-Filho, Jorge S., Geyer, Charles E., Wen, Hannah Y.

المساهمون: Williams Family Chair in Breast Oncology, Breast Cancer Research Foundation, U.S. Department of Health & Human Services | NIH | National Cancer Institute

المصدر: npj Breast Cancer ; volume 9, issue 1 ; ISSN 2374-4677

مصطلحات موضوعية: Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Oncology

الوصف: Rare subtypes of triple-negative breast cancers (TNBC) are a heterogenous group of tumors, comprising 5–10% of all TNBCs. Despite accounting for an absolute number of cases in aggregate approaching that of other less common, but well studied solid tumors, rare subtypes of triple-negative disease remain understudied. Low prevalence, diagnostic challenges and overlapping diagnoses have hindered consistent categorization of these breast cancers. Here we review epidemiology, histology and clinical and molecular characteristics of metaplastic, triple-negative lobular, apocrine, adenoid cystic, secretory and high-grade neuroendocrine TNBCs. Medullary pattern invasive ductal carcinoma no special type, which until recently was a considered a distinct subtype, is also discussed. With this background, we review how applying biological principals often applied to study TNBC no special type could improve our understanding of rare TNBCs. These could include the utilization of targeted molecular approaches or disease agnostic tools such as tumor mutational burden or germline mutation-directed treatments. Burgeoning data also suggest that pathologic response to neoadjuvant therapy and circulating tumor DNA have value in understanding rare subtypes of TNBC. Finally, we discuss a framework for advancing disease-specific knowledge in this space. While the conduct of randomized trials in rare TNBC subtypes has been challenging, re-envisioning trial design and technologic tools may offer new opportunities. These include embedding rare TNBC subtypes in umbrella studies of rare tumors, retrospective review of contemporary trials, prospective identification of patients with rare TNBC subtypes entering on clinical trials and querying big data for outcomes of patients with rare breast tumors.

الإتاحة: https://doi.org/10.1038/s41523-023-00554-xTest
https://www.nature.com/articles/s41523-023-00554-x.pdfTest
https://www.nature.com/articles/s41523-023-00554-xTest

المؤلفون: Advani, Pooja P., Ruddy, Kathryn J., Herrmann, Joerg, Ray, Jordan C., Craver, Emily C., Yothers, Greg, Cecchini, Reena S., Lipchik, Corey, Feng, Huichen, Rastogi, Priya, Mamounas, Eleftherios P., Swain, Sandra M., Geyer, Charles E., Wolmark, Norman, Paik, Soonmyung, Pogue-Geile, Katherine L., Colon-Otero, Gerardo, Perez, Edith A., Norton, Nadine

المصدر: Frontiers in Oncology ; volume 13 ; ISSN 2234-943X

الوصف: Background The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity. Methods Using the Agena Bioscience MassARRAY system, we genotyped TRPC6 rs77679196, BRINP1 rs62568637, LDB2 rs55756123, RAB22A rs707557, intergenic rs4305714, LINC01060 rs7698718, and CBR3 rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzumab) in 993 patients with HER2+ early breast cancer from the NSABP B-31 trial of adjuvant anthracycline-based chemotherapy ± trastuzumab. Association analyses were performed with outcomes of congestive heart failure ( N = 29) and maximum decline in left ventricular ejection fraction (LVEF) using logistic and linear regression models, respectively, under an additive model with age, baseline LVEF, and previous use of hypertensive medications as covariates. Results Associations of maximum decline in LVEF in the NCCTG N9831 patients did not replicate in the NSABP B-31 patients. However, TRPC6 rs77679196 and CBR3 rs1056892 were significantly associated with congestive heart failure, p < 0.05, with stronger associations observed in patients treated with chemotherapy only (no trastuzumab) or in the combined analysis of all patients relative to those patients treated with chemotherapy + trastuzumab. Conclusions TRPC6 rs77679196 and CBR3 rs1056892 (V244M) are associated with doxorubicin-induced cardiac events in both NCCTG N9831 and NSABP B-31. Other variants previously associated with trastuzumab-related decline in LVEF failed to replicate between these studies.

الإتاحة: https://doi.org/10.3389/fonc.2023.1139347Test

المؤلفون: Ganz, Patricia A, Romond, Edward H, Cecchini, Reena S, Rastogi, Priya, Geyer, Charles E, Swain, Sandra M, Jeong, Jong-Hyeon, Fehrenbacher, Louis, Gross, Howard M, Brufsky, Adam M, Flynn, Patrick J, Wahl, Tanya A, Seay, Thomas E, Wade, James L, Biggs, David D, Atkins, James N, Polikoff, Jonathan, Zapas, John L, Mamounas, Eleftherios P, Wolmark, Norman

المصدر: Journal of Clinical Oncology. 35(35)

مصطلحات موضوعية: Clinical Research, Patient Safety, Breast Cancer, Cancer, Heart Disease, Clinical Trials and Supportive Activities, Prevention, Cardiovascular, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cancer Survivors, Cardiovascular System, Chemotherapy, Adjuvant, Cohort Studies, Cyclophosphamide, Doxorubicin, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Middle Aged, Paclitaxel, Quality of Life, Receptor, ErbB-2, Trastuzumab, Ventricular Dysfunction, Left, Receptor, erbB-2, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment. Patients and Methods Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2-positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions. Results At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a > 10% decline in left ventricular ejection fraction from baseline to a value < 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab. Conclusion In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6nw5d3gxTest

المؤلفون: Bear, Harry D, Tang, Gong, Rastogi, Priya, Geyer, Charles E, Zoon, Christine K, Kidwell, Kelley M, Robidoux, André, Baez-Diaz, Luis, Brufsky, Adam M, Mehta, Rita S, Fehrenbacher, Louis, Young, James A, Senecal, Francis M, Gaur, Rakesh, Margolese, Richard G, Adams, Paul T, Gross, Howard M, Costantino, Joseph P, Paik, Soonmyung, Swain, Sandra M, Mamounas, Eleftherios P, Wolmark, Norman

المصدر: Annals of Surgical Oncology. 24(7)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Trials and Supportive Activities, Cancer, Breast Cancer, Clinical Research, Patient Safety, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Anthracyclines, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Breast Neoplasms, Combined Modality Therapy, Docetaxel, Female, Follow-Up Studies, Humans, Mammaplasty, Mastectomy, Prognosis, Prospective Studies, Surgical Wound Infection, Survival Rate, Taxoids, Oncology & Carcinogenesis, Oncology and carcinogenesis

الوصف: BackgroundNRG Oncology/NSABP trial B-40 tested the impact of adding bevacizumab (bev) to neoadjuvant chemotherapy for operable breast cancer. Secondary endpoints included rates of surgical complications after surgery in patients who did or did not receive bev.MethodsA total of 1206 women with HER2-negative operable breast cancer were randomly assigned to receive one of three different docetaxel-plus-anthracycline-based regimens, without or with bev (15 mg/kg every 3 weeks) for the first 6 of 8 cycles and for 10 doses postoperatively. Surgical complications were assessed from date of surgery through 24 months following study entry.ResultsEarly surgical complications were significantly more frequent in the bev group (25.4 vs. 18.9%; trend test p = 0.008), but most were grade 1-2. Early noninfectious wound dehiscences were infrequent and not significantly different (5.4 vs. 3.1%; trend test p = 0.15). Long-term noninfectious wound complications were significantly higher for patients receiving bev (11.8 vs. 5.1%; trend test p = 0.0007), but the incidence of grade ≥3 wound dehiscence was low in both groups (

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9h41p0rtTest

المؤلفون: Loibl, Sibylle, Huang, Chiun-Sheng, Mano, Max S., Mamounas, Eleftherios P., Geyer, Charles E., Untch, Michael, Thery, Jean-Christophe, Schwaner, Ingo, Limentani, Steven, Loman, Niklas, Lübbe, Kristina, Chang, Jenny C., Hatschek, Thomas, Tesarowski, David, Song, Chunyan, Lysbet de Haas, Sanne, Boulet, Thomas, Lambertini, Chiara, Wolmark, Norman

المساهمون: Roche

المصدر: npj Breast Cancer ; volume 8, issue 1 ; ISSN 2374-4677

مصطلحات موضوعية: Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Oncology

الوصف: Following chemotherapy and human epidermal growth factor 2 (HER2)-targeted neoadjuvant therapy for HER2-positive early breast cancer, residual invasive breast cancer at surgery may be HER2-negative on retesting in some patients. We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the pre-treatment core biopsy with HER2-negative central testing on their corresponding surgical specimen after neoadjuvant treatment. In the 70/845 (8.3%) patients with HER2-negative residual disease on retesting at surgery, there were 11 IDFS events in the 42 trastuzumab-treated patients (26.2%) and none in the 28 T-DM1-treated patients, suggesting that T-DM1 should not be withheld in this patient population.

الإتاحة: https://doi.org/10.1038/s41523-022-00477-zTest
https://www.nature.com/articles/s41523-022-00477-z.pdfTest
https://www.nature.com/articles/s41523-022-00477-zTest

المؤلفون: Mamounas, Eleftherios P, Bandos, Hanna, Rastogi, Priya, Lembersky, Barry C, Jeong, Jong-Hyeon, Geyer, Charles E, Fehrenbacher, Louis, Chia, Stephen K, Brufsky, Adam M, Walshe, Janice M, Soori, Gamini S, Dakhil, Shaker R, Wade, James L, McCarron, Edward C, Swain, Sandra M, Wolmark, Norman

المصدر: JNCI: Journal of the National Cancer Institute; Nov2023, Vol. 115 Issue 11, p1302-1309, 8p

مصطلحات موضوعية: CLINICAL trials, BREAST cancer, LETROZOLE, SECONDARY primary cancer, CANCER relapse

مستخلص: Background The National Surgical Adjuvant Breast and Bowel Project B-42 trial evaluated extended letrozole therapy (ELT) in postmenopausal breast cancer patients who were disease free after 5 years of aromatase inhibitor (AI)–based therapy. Seven-year results demonstrated a nonstatistically significant trend in disease-free survival (DFS) in favor of ELT. We present 10-year outcome results. Methods In this double-blind, phase III trial, patients with stage I-IIIA hormone receptor–positive breast cancer, disease free after 5 years of an AI or tamoxifen followed by an AI, were randomly assigned to 5 years of letrozole or placebo. Primary endpoint was DFS, defined as time from random assignment to breast cancer recurrence, second primary malignancy, or death. All statistical tests are 2-sided. Results Between September 2006 and January 2010, 3966 patients were randomly assigned (letrozole: 1983; placebo: 1983). Median follow-up time for 3923 patients included in efficacy analyses was 10.3 years. There was statistically significant improvement in DFS in favor of letrozole compared with placebo (hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.74 to 0.96; P  = .01; 10-year DFS: placebo = 72.6%, letrozole = 75.9%, absolute difference = 3.3%). There was no difference in the effect of letrozole on overall survival (HR = 0.97, 95% CI = 0.82 to 1.15; P  = .74). Letrozole statistically significantly reduced breast cancer–free interval events (HR = 0.75, 95% CI = 0.62 to 0.91; P  = .003; absolute difference in cumulative incidence = 2.7%) and distant recurrences (HR = 0.72, 95% CI = 0.55 to 0.92; P  = .01; absolute difference = 1.8%). The rates of osteoporotic fractures and arterial thrombotic events did not differ between treatment groups. Conclusions The beneficial effect of ELT on DFS persisted at 10 years. Letrozole also improved breast cancer–free interval and distant recurrences without improving overall survival. Careful assessment of potential risks and benefits is necessary for selecting appropriate candidates for ELT. [ABSTRACT FROM AUTHOR]

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المؤلفون: Metzger-Filho, Otto, Collier, Katharine, Asad, Sarah, Ansell, Peter J., Watson, Mark, Bae, Junu, Cherian, Mathew, O’Shaughnessy, Joyce, Untch, Michael, Rugo, Hope S., Huober, Jens B., Golshan, Mehra, Sikov, William M., von Minckwitz, Gunter, Rastogi, Priya, Li, Lang, Cheng, Lijun, Maag, David, Wolmark, Norman, Denkert, Carsten, Symmans, W. Fraser, Geyer, Charles E., Loibl, Sibylle, Stover, Daniel G.

المساهمون: Alliance Foundation [to D.G.S.] and Breast Cancer Research Foundation [to D.G.S.], Conquer Cancer Foundation

المصدر: npj Breast Cancer ; volume 7, issue 1 ; ISSN 2374-4677

مصطلحات موضوعية: Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Oncology

الوصف: In the BrighTNess trial, carboplatin added to neoadjuvant chemotherapy (NAC) was associated with increased pathologic complete response (pCR) rates in patients with stage II/III triple-negative breast cancer (TNBC). In this matched cohort study, cases with a germline BRCA1/2 mutation (gBRCA; n = 75) were matched 1:2 with non-gBRCA controls ( n = 150) by treatment arm, lymph node status, and age to evaluate pCR rates and association of benefit from platinum/PARP inhibitors with validated RNA expression-based immune, proliferation, and genomic instability scores among gBRCA with the addition of carboplatin ± veliparib to NAC. Among the well-matched cohorts, odds of pCR were not higher in gBRCA cancers who received standard NAC with carboplatin (OR 0.24, 95% CI [0.04-1.24], p = 0.09) or with carboplatin/veliparib (OR 0.44, 95% CI [0.10-1.84], p = 0.26) compared to non-gBRCA cancers. Higher PAM50 proliferation, GeparSixto immune, and CIN70 genomic instability scores were each associated with higher pCR rate in the overall cohort, but not specifically in gBRCA cases. In this study, gBRCA carriers did not have higher odds of pCR than non-gBRCA controls when carboplatin ± veliparib was added to NAC, and showed no significant differences in molecular, immune, chromosomal instability, or proliferation gene expression metrics.

الإتاحة: https://doi.org/10.1038/s41523-021-00349-yTest
https://www.nature.com/articles/s41523-021-00349-y.pdfTest
https://www.nature.com/articles/s41523-021-00349-yTest