scholarly journals Neoadjuvant endocrine treatment of women with breast cancer

2011 ◽  
Vol 5 (3) ◽  
pp. 157
Author(s):  
Julian Iturbe ◽  
Ariel Zwenger ◽  
Carlos Vallejo ◽  
Bernardo Leone ◽  
Pablo Leone

Neoadjuvant therapy has four goals in breast cancer: decrease tumor volume to operate tumors that initially were inoperable, increase the number of conservative surgeries, evaluate the chemosensitivity in vivo and analyze the management of micrometastases. Neoadjuvant treatment provides a unique setting in which we can monitor clinical, pathological, proliferative and molecular responses. Combining different strategies such us surgery, radiation therapy, chemotherapy, and endocrine therapy has contributed substantially to the survival improvement in breast cancer. Thirdgeneration aromatase inhibitors have proven to be superior to tamoxifen in the adjuvant and, more recently, the neoadjuvant treatment of postmenopausal patients. The need to define how to select the patients that will benefit the most from these therapies, the optimal duration of treatment, the bestmethod to evaluate the treatment response, the identification of predictive factors for response, and the superiority of certain endocrine agents over others have been reviewed. We have carried out a critical analysis of the current literature on the utilization of endocrine therapy in the neoadjuvant setting for breast cancer. This review discusses the current evidence regarding primary endocrine therapy and the current opinions on length of treatment and measurement of response prior to surgery.

2011 ◽  
pp. 157-166
Author(s):  
Julian Iturbe ◽  
Ariel Zwenger ◽  
Carlos Vallejo ◽  
Bernardo Leone ◽  
Pablo Leone

Neoadjuvant therapy has four goals in breast cancer: decrease tumor volume to operate tumors that initially were inoperable, increase the number of conservative surgeries, evaluate the chemosensitivity in vivo and analyze the management of micrometastases. Neoadjuvant treatment provides a unique setting in which we can monitor clinical, pathological, proliferative and molecular responses. Combining different strategies such us surgery, radiation therapy, chemotherapy, and endocrine therapy has contributed substantially to the survival improvement in breast cancer. Thirdgeneration aromatase inhibitors have proven to be superior to tamoxifen in the adjuvant and, more recently, the neoadjuvant treatment of postmenopausal patients. The need to define how to select the patients that will benefit the most from these therapies, the optimal duration of treatment, the bestmethod to evaluate the treatment response, the identification of predictive factors for response, and the superiority of certain endocrine agents over others have been reviewed. We have carried out a critical analysis of the current literature on the utilization of endocrine therapy in the neoadjuvant setting for breast cancer. This review discusses the current evidence regarding primary endocrine therapy and the current opinions on length of treatment and measurement of response prior to surgery.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 518-518
Author(s):  
Frederik Marmé ◽  
Miguel Martin ◽  
Michael Untch ◽  
Herve R. Bonnefoi ◽  
Sung-Bae Kim ◽  
...  

518 Background: PENELOPE-B assessed efficacy of the CDK4/6 inhibitor 1-year palbociclib versus placebo added to endocrine therapy (ET) as post-neoadjuvant treatment in a high-risk breast cancer population. Palbociclib did not improve invasive disease-free survival (iDFS) compared to placebo (3-year iDFS 81.3% vs 77.7%) (Loibl et al. J Clin Oncol 2021). Here we report results from the subpopulation of premenopausal women. Methods: Patients with hormone receptor positive, HER2-negative breast cancer without pathological complete response after taxane‐containing neoadjuvant chemotherapy and at high risk of relapse (CPS‐EG score ≥3 or 2 and ypN+) were randomized (1:1) to receive 13 cycles of palbociclib 125mg daily or placebo on days 1-21 in a 28d cycle in addition to standard endocrine treatment including tamoxifen (TAM) +/- gonadotropin-releasing hormone analogue (GnRH) and aromatase inhibitor (AI) +/- GnRH. Randomization was stratified by nodal status at surgery, age ( < 50 vs ≥50 years), Ki-67, region, and CPS-EG score. Results: 616/1250 patients were premenopausal at the time of enrollment, 185 of these patients (30.0%) were younger than 40 years of age. 95.2% had ypN+ after surgery; 42.8% had ypT2 and 46.8% a CPS-EG score of 3. 23.1% of the premenopausal women had a Ki67 of > 15% in residual disease. 66.1% started with TAM alone; 19.3% with TAM and ovarian function suppression (OFS); and 13.6% received an AI+OFS. There was no difference in iDFS between palbociclib and placebo in the premenopausal women HR 0.948 (0.693-1.30). The 3-year iDFS was 80.6% and 78.3%, respectively. Palbociclib vs placebo in subgroups by endocrine treatment: TAM alone HR 1.05 (0.715-1.53) p = 0.817; TAM+GnRH HR 0.52 (0.267-1.02) p = 0.057 and AI+GnRH HR 1.58 (0.548-4.56) p = 0.397; pinteraction0.124. Hematologic toxicity was significantly more common with palbociclib. Non-hematological toxicity any grade palbociclib vs placebo were: fatigue 67.4% vs 51.3%; hot flushes 52.2% vs 54.8%; bone pain 15.6% vs 16.6%; and vaginal dryness 11.0% vs 11.5%. When receiving palbociclib fewer patients in the AI+GnRH group vs the TAM +/- GnRH cohort experienced anemia (54.1% vs 80.5%) and thrombocytopenia (37.8% vs 65.1%). Fatigue (75.7% vs 66.3%) and nausea (40.5% vs 24.9%) were more common with AI+GnRH than TAM +/-GnRH when palbociclib was added. Thromboembolic events were low with overall 9 events (4 vs 5; AI+GnRH 2.4% vs 1.3% TAM+/-GnRH). Conclusions: The addition of palbociclib to endocrine therapy did not improve iDFS in premenopausal women. These are the first safety results from a phase III study for the combination tamoxifen +/-GnRH and palbociclib. The addition of palbociclib to tamoxifen +/-GnRH in premenopausal women did not increase side effects compared to AI+GnRH and seems to be an alternative to AI+GnRH. Clinical trial information: NCT01864746.


Author(s):  
Tazia Irfan ◽  
Mainul Haque ◽  
Sayeeda Rahman ◽  
Russell Kabir ◽  
Nuzhat Rahman ◽  
...  

Breast cancer remains one of the major causes of death in women, and endocrine treatment is currently one of the mainstay of treatment in patients with estrogen receptor positive breast cancer. Endocrine therapy either slows down or stops the growth of hormone-sensitive tumors by blocking the body’s capability to yield hormones or by interfering with hormone action. In this paper, we intended to review various approaches of endocrine treatments for breast cancer highlighting successes and limitations. There are three settings where endocrine treatment of breast cancer can be used: neoadjuvant, adjuvant, or metastatic. Several strategies have also been developed to treat hormone-sensitive breast cancer which include ovarian ablation, blocking estrogen production, and stopping estrogen effects. Selective estrogen-receptor modulators (SERMs) (e.g. tamoxifen and raloxifene), aromatase inhibitors (AIs) (e.g. anastrozole, letrozole and exemestane), gonadotropin-releasing hormone agonists (GnRH) (e.g. goserelin), and selective estrogen receptor downregulators (SERDs) (e.g. fulvestrant) are currently used drugs to treat breast cancer. Tamoxifen is probably the first targeted therapy widely used in breast cancer treatment which is considered to be very effective as first line endocrine treatment in previously untreated patients and also can be used after other endocrine therapy and chemotherapy. AIs inhibit the action of enzyme aromatase which ultimately decrease the production of estrogen to stimulate the growth of ER+ breast cancer cells. GnRH agonists suppress ovarian function, inducing artificial menopause in premenopausal women. Endocrine treatments are cheap, well-tolerated and have a fixed single daily dose for all ages, heights and weights of patients. Endocrine treatments are not nearly as toxic as chemotherapy and frequent hospitalization can be avoided. New drugs in preliminary trials demonstrated the potential for improvement of the efficacy of endocrine therapy including overcoming resistance. However, the overall goals for breast cancer including endocrine therapy should focus on effective control of cancer, design personalized medical therapeutic approach, increase survival time and quality of life, and improve supportive and palliative care for end-stage disease.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sanne Løkkegaard ◽  
Daniel Elias ◽  
Carla L. Alves ◽  
Martin V. Bennetzen ◽  
Anne-Vibeke Lænkholm ◽  
...  

AbstractResistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1655
Author(s):  
Cinzia Solinas ◽  
Debora Fumagalli ◽  
Maria Vittoria Dieci

The present commentary synthesizes the current evidence on the role of the immune response in HER2-positive breast cancer. It points out the strengths and weaknesses of the findings observed so far, particularly in the early setting, including the clinical significance of scoring tumor-infiltrating lymphocytes. A figure proposing research hypotheses for the implementation of immune checkpoint blockade use for patient candidates to neoadjuvant treatment is presented.


The Breast ◽  
2011 ◽  
Vol 20 (4) ◽  
pp. 365-369 ◽  
Author(s):  
M.J. Traa ◽  
C.M.E.M. Meijs ◽  
M.A.C. de Jongh ◽  
E.C.H.M. van der Borst ◽  
J.A. Roukema

2017 ◽  
Vol 26 (12) ◽  
pp. 2094-2100 ◽  
Author(s):  
Maria Burton ◽  
Karen Kilner ◽  
Lynda Wyld ◽  
Kate Joanna Lifford ◽  
Frances Gordon ◽  
...  

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