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Pepi Breast Cancer

Tomás Reinert, Rodrigo Gonçalves, Matthew J Ellis
Neoadjuvant endocrine therapy (NET) with Ki67-based response monitoring is a practical, cost-effective approach to the management of clinical stage II and III estrogen receptor-positive (ER+) breast cancer. In addition to marked improvements in rates of breast conservation, the identification of extreme responders on the basis of the preoperative endocrine prognostic index (PEPI) provides a rationale to avoid chemotherapy on the basis of highly favorable prognosis in some patients. Finally, samples accrued from patients treated with neoadjuvant therapy are providing valuable insights into the molecular basis for intrinsic resistance to endocrine therapy and promise a more rational basis and precise approach to the systemic treatment of ER+ breast cancer...
April 16, 2018: Current Treatment Options in Oncology
Angel Guerrero-Zotano, Thomas Stricker, Luigi Formisano, Katherine E Hutchinson, Daniel G Stover, Kyung-Min Lee, Luis J Schwarz, Jennifer M Giltnane, Monica V Estrada, Valerie M Jansen, Alberto Servetto, Joaquín Gavilá, José Alejandro Pérez-Fidalgo, Ana Lluch, Antonio Llombart-Cussac, Mohamed Amine Bayar, Stefan Michiels, Fabrice Andre, Monica Arnedos, Vicente Guillem, Amparo Ruiz-Simon, Carlos L Arteaga
PURPOSE: This study aimed to identify biomarkers of resistance to endocrine therapy in ER+ breast cancers (BC) treated with prolonged neoadjuvant letrozole. Experimental Design: We performed targeted DNA and RNA-sequencing in 68 ER+ BC from patients treated with preoperative letrozole (median 7 months). Results:Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC>1, FDR<0...
March 26, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Takayuki Ueno, Shigehira Saji, Norikazu Masuda, Katsumasa Kuroi, Nobuaki Sato, Hiroyuki Takei, Yutaka Yamamoto, Shinji Ohno, Hiroko Yamashita, Kazufumi Hisamatsu, Kenjiro Aogi, Hiroji Iwata, Takeharu Yamanaka, Hironobu Sasano, Masakazu Toi
Background: Neoadjuvant endocrine therapy (NET) has been demonstrated to improve breast-conserving rate and is a widely accepted treatment option for postmenopausal patients with hormone receptor-positive breast cancer. There are few reports on the association of NET response and long-term outcomes. Objectives: To investigate the prognostic value of clinical response to NET. Methods: Long-term outcomes of NET were examined in 107 patients who participated in the multicentre prospective neoadjuvant exemestane study, JFMC34-0601...
2018: ESMO Open
Louis W C Chow, Satoshi Morita, Christopher Y C Chow, Wai-Kuen Ng, Masakazu Toi
The purpose of the study was to test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2-ve invasive breast cancer, 2 cm or greater, were enrolled in an open-label, single-arm study. Twenty eligible patients were given letrozole 2.5 mg per day together with palbociclib 125 mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery...
February 2018: Endocrine-related Cancer
Matthew J Ellis
For post-menopausal women with clinical stage II/III estrogen receptor positive (ER+) breast cancer neoadjuvant endocrine therapy (NET) is an under-utilized and low-toxicity alternative to chemotherapy for increasing breast conservation rates. Individual responses to endocrine therapy can also be used to tailor systemic treatment. The Preoperative Endocrine Prognostic Index (PEPI) was developed to identify patients at low risk of relapse after NET so that adjuvant chemotherapy can safely be avoided. In a recent validation study, patients with pathological stage 1 or 2A breast cancers with a Ki67 value of 2...
August 2017: Breast: Official Journal of the European Society of Mastology
Hans-Christian Kolberg, Bahriye Aktas, Cornelia Liedtke
Primary endocrine therapy is an option in cases of hormone receptor positive and HER2 negative non-metastatic breast cancer. Aromatase inhibitors are considered the therapy of choice in postmenopausal patients. In premenopausal patients aromatase inhibitors in combination with LHRHanalogues are regarded superior to tamoxifen. Three different settings have to be discriminated: • Patients too frail for surgery are candidates for primary endocrine therapy in order to control the disease. Treatment duration is determined by the course of the disease...
2017: Reviews on Recent Clinical Trials
Matthew J Ellis, Vera J Suman, Jeremy Hoog, Rodrigo Goncalves, Souzan Sanati, Chad J Creighton, Katherine DeSchryver, Erika Crouch, Amy Brink, Mark Watson, Jingqin Luo, Yu Tao, Michael Barnes, Mitchell Dowsett, G Thomas Budd, Eric Winer, Paula Silverman, Laura Esserman, Lisa Carey, Cynthia X Ma, Gary Unzeitig, Timothy Pluard, Pat Whitworth, Gildy Babiera, J Michael Guenther, Zoneddy Dayao, David Ota, Marilyn Leitch, John A Olson, D Craig Allred, Kelly Hunt
Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole...
April 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Belinda Yeo, Mitch Dowsett
Neoadjuvant endocrine treatment has become of increasing interest for downstaging primary ER+ breast cancers as it has become clear that the pathologic complete response rate of luminal tumours to chemotherapy is much lower than that of non-luminal and differs little from that to endocrine therapy. There is much more experience in postmenopausal than premenopausal women. Aromatase inhibitors are generally the agent of choice. Responses are lower in those with the low levels of ER. While duration of endocrine treatment in clinical trials has usually been standardized at around three to four months it is clear that volume reductions continue to occur beyond that time in a large proportion of cases and routine clinical practice is often to treat to maximum response...
November 2015: Breast: Official Journal of the European Society of Mastology
Arlette Elizalde, Luis Pina, Jon Etxano, Pedro Slon, Romina Zalazar, Meylin Caballeros
BACKGROUND: Digital mammography (DM) is widespread used for the detection of breast cancer, but its sensitivity drops in dense breasts. It is well known that additional breast ultrasound (US) and digital breast tomosynthesis (DBT) increase the sensitivity of DM. However, to our knowledge, there are no articles comparing the role of both additional techniques. PURPOSE: To assess the diagnostic performance of DM and the different combinations of DM + additional DBT and DM + additional US in an enriched sample of patients...
January 2016: Acta Radiologica
Matthew J Ellis, Vera J Suman, Jeremy Hoog, Li Lin, Jacqueline Snider, Aleix Prat, Joel S Parker, Jingqin Luo, Katherine DeSchryver, D Craig Allred, Laura J Esserman, Gary W Unzeitig, Julie Margenthaler, Gildy V Babiera, P Kelly Marcom, Joseph M Guenther, Mark A Watson, Marilyn Leitch, Kelly Hunt, John A Olson
PURPOSE: Preoperative aromatase inhibitor (AI) treatment promotes breast-conserving surgery (BCS) for estrogen receptor (ER)-positive breast cancer. To study this treatment option, responses to three AIs were compared in a randomized phase II neoadjuvant trial designed to select agents for phase III investigations. PATIENTS AND METHODS: Three hundred seventy-seven postmenopausal women with clinical stage II to III ER-positive (Allred score 6-8) breast cancer were randomly assigned to receive neoadjuvant exemestane, letrozole, or anastrozole...
June 10, 2011: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Masakazu Toi, Shigehira Saji, Norikazu Masuda, Katsumasa Kuroi, Nobuaki Sato, Hiroyuki Takei, Yutaka Yamamoto, Shinji Ohno, Hiroko Yamashita, Kazufumi Hisamatsu, Kenjiro Aogi, Hiroji Iwata, Masahiro Takada, Takayuki Ueno, Shigetoyo Saji, Niramol Chanplakorn, Takashi Suzuki, Hironobu Sasano
Aromatase inhibitor shows efficacy for hormone receptor positive postmenopausal breast cancer. We evaluated the activity of 24 weeks of aromatase inhibition with exemestane for primary breast cancer in a neoadjuvant setting. Patients with stage II/IIIA invasive breast cancer with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive status were eligible. Primary endpoints were objective response rate (ORR) and safety. A steroidal aromatase inhibitor exemestane of 25 mg/day was administered for 16 weeks with an 8-week extension...
April 2011: Cancer Science
Masakazu Toi, Hironobu Sasano, Matthew J Ellis
Third-generation aromatase inhibitors(AIs)have recently overtaken tamoxifen(TAM)to play a key role in the adjuvant treatment of post-menopausal hormone receptor-positive breast cancer patients. The accumulating evidence of neoadjuvant chemotherapy is now contributing to growing interest in neoadjuvant endocrine therapy using AIs. Recent research has revealed that administration of AIs 3-4 months prior to surgery is more effective than TAM in terms of the clinical response rate and the breast-conserving surgical procedure rate...
June 2009: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Cynthia X Ma, Cesar G Sanchez, Matthew J Ellis
Endocrine therapy is one of the most effective treatment strategies for breast cancer. However, in the adjuvant setting, up to 40% to 50% of patients with estrogen receptor (ER)-positive breast cancers relapse despite these interventions. Although ER and HER2 analysis has increased our ability to predict which patients will benefit from endocrine therapy, further improvement is needed, most specifically for patients with ER-positive, HER2-negative disease. Recent advances in genomic technology have made it possible to classify breast cancers into risk categories with significant prognostic implications...
February 2009: Oncology (Williston Park, NY)
Matthew J Ellis, Yu Tao, Jingqin Luo, Roger A'Hern, Dean B Evans, Ajay S Bhatnagar, Hilary A Chaudri Ross, Alexander von Kameke, William R Miller, Ian Smith, Wolfgang Eiermann, Mitch Dowsett
BACKGROUND: Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine treatment for estrogen receptor-positive (ER+) breast cancer. METHODS: Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial, which compared letrozole and tamoxifen for 4 months before surgery, were analyzed for posttreatment ER status, Ki67 proliferation index, histological grade, pathological tumor size, node status, and treatment response...
October 1, 2008: Journal of the National Cancer Institute
Gail A Greendale, Mei-Hua Huang, Giske Ursin, Sue Ingles, Frank Stanczyk, Carolyn Crandall, Gail A Laughlin, Elizabeth Barrett-Connor, Arun Karlamangla
BACKGROUND: Prolactin is a polypeptide hormone that promotes normal breast proliferation and differentiation, but it is also implicated in the development and growth of mammary tumors. Mammographic density is a strong, independent predictor of breast cancer and, therefore, a potential surrogate indicator of breast cancer risk. METHODS: To test the hypothesis that serum prolactin is positively related to mammographic density, we conducted a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Mammographic Density Study...
November 2007: Breast Cancer Research and Treatment
Gianfilippo Bertelli, Ornella Garrone, Marco Merlano, Marcella Occelli, Laura Bertolotti, Federico Castiglione, Fiorella Pepi, Ornella Fusco, Lucia Del Mastro, Robert C F Leonard
BACKGROUND: The steroidal aromatase inactivator exemestane has demonstrated activity after prior failure of non-steroidal aromatase inhibitors (including third-generation inhibitors letrozole and anastrozole) in postmenopausal women with advanced breast cancer. If exemestane is used as first anti-aromatase agent, however, it is unclear whether patients can still benefit from letrozole or anastrozole after progression. PATIENTS AND METHODS: Postmenopausal patients with advanced, hormone receptor-positive or -unknown breast cancer were eligible for this study...
2005: Oncology
Carolyn Crandall, Shana Palla, Beth A Reboussin, Giske Ursin, Gail A Greendale
INTRODUCTION: Mammographic breast density is a strong independent risk factor for breast cancer. We hypothesized that demonstration of an association between mammographic breast density and bone mineral density (BMD) would suggest a unifying underlying mechanism influencing both breast density and BMD. METHODS: In a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions Study (PEPI), participants were aged 45 to 64 years and were at least 1 year postmenopausal...
2005: Breast Cancer Research: BCR
Gail A Greendale, Shana L Palla, Giske Ursin, Gail A Laughlin, Carolyn Crandall, Malcolm C Pike, Beth A Reboussin
Mammographic density is an independent risk factor for breast cancer. In postmenopausal women, higher levels of endogenous sex steroids are associated with an increased risk of breast cancer. Limited prior data suggest that endogenous sex steroids either are not associated (total estradiol and progesterone) or are negatively associated (free estradiol) with higher mammographic density. To analyze the associations between endogenous sex steroids and mammographic density, the authors conducted a 1998-2005 cross-sectional analysis of baseline clinical trial data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial for US women who had not used hormone therapy for at least 3...
November 1, 2005: American Journal of Epidemiology
Malcolm C Pike
The Women's Health Initiative (WHI) study showed that postmenopausal continuous combined estrogen-progestogen therapy (EPT) significantly increases the risk of breast cancer, thus confirming the results from large epidemiological studies. These results were predicted approximately 15 years previously based on the epidemiology of breast cancer and the relationship of ovarian hormone levels to breast cell proliferation. However, the prediction had little effect on prescribing habits due to its theoretical nature...
July 2005: Gynecological Endocrinology
Giske Ursin, Shana L Palla, Beth A Reboussin, Stacey Slone, Carol Wasilauskas, Malcolm C Pike, Gail A Greendale
PURPOSE: Postmenopausal estrogen and progestin therapy (EPT) increases mammographic percent density and breast cancer risk substantially more than does estrogen therapy alone. We determined whether increases in serum estrone as a function of treatment predict increases in mammographic percent density. METHODS: We measured mammographic percent density and serum estrone levels in participants in the Postmenopausal Estrogen/Progestin Interventions Trial who were randomly assigned to receive conjugated equine estrogens (CEE) 0...
July 15, 2004: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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