scholarly journals Preoperative endocrine therapy for breast cancer.

2000 ◽  
pp. 131-141 ◽  
Author(s):  
K L Cheung ◽  
A Howell ◽  
J F Robertson

The preoperative use of systemic therapy for primary breast cancer has the potential to downstage tumours. This would render suitable for breast conservation some tumours that were unsuitable at initial presentation, or would convert some inoperable locally advanced breast cancers into tumours that are operable. No survival benefit has been demonstrated for neoadjuvant chemotherapy compared with the same therapy given in an adjuvant setting. Preoperative endocrine therapy, in contrast to neoadjuvant chemotherapy, has fewer side effects and has the potential additional advantage that it can be continued throughout the perioperative period. Current data have shown that, in patients with an oestrogen receptor (ER)-positive tumour, a response approaching 70% could be reached in approximately 3 months using traditional endocrine manipulation such as tamoxifen. Randomised clinical trials are warranted to demonstrate the superiority of preoperative endocrine therapy over conventional adjuvant endocrine therapy, to define the optimum duration of therapy, and to identify the best endocrine agents. Both clinical and laboratory studies are also required to identify factors (in addition to ER) that would precisely predict the response and hence to select appropriate patients and to improve existing methods of monitoring response.

Author(s):  
Tomás Reinert ◽  
Susana Ramalho ◽  
Rodrigo Gonçalves ◽  
Carlos Barrios ◽  
Marcia Graudenz ◽  
...  

AbstractBreast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.


1987 ◽  
Vol 5 (11) ◽  
pp. 1779-1782 ◽  
Author(s):  
U Berger ◽  
J L Mansi ◽  
P Wilson ◽  
R C Coombes

We devised a method of detecting estrogen receptors (ER) in bone marrow metastases from patients with breast cancer. The method involves a sequential double-staining immunocytochemical technique, with a monoclonal antibody to ER and a polyclonal antibody recognizing epithelial membrane antigen to confirm the epithelial nature of suspected tumor cells. Twenty-seven patients were assessed: ten were found to have ER-positive tumor cells in the bone marrow; ten had ER-negative cells; and the remaining seven patients had no tumor cells in the bone marrow smears. Of the ten patients with ER-positive cells, eight (80%) either had a response to endocrine therapy, implying that they possess ER-positive breast cancers, or had ER-positive primary tumors as determined by the dextran-coated charcoal biochemical assay (DCC). Of the ten patients with ER-negative cells in the bone marrow, eight failed to respond to endocrine therapy. This technique therefore provides a means of predicting which patients will respond to endocrine therapy, and is particularly important in those patients whose ER status is unknown.


2019 ◽  
Vol 19 (6) ◽  
pp. e683-e689 ◽  
Author(s):  
Nathalie LeVasseur ◽  
Kaylie-Anne Willemsma ◽  
Huaqi Li ◽  
Lovedeep Gondara ◽  
Walter C. Yip ◽  
...  

2018 ◽  
Vol 17 (3) ◽  
pp. 11-19
Author(s):  
V. F. Semiglazov ◽  
V. V. Semiglazov ◽  
G. A. Dashyan ◽  
P. V. Krivorotko ◽  
V. G. Ivanov ◽  
...  

More than 70 % of patients with breast cancer have estrogen-receptor-positive tumors (ER+) and are considered hormone- sensitive. That is why a vast majority of patients with early operable  tumors receive adjuvant endocrine therapy. Patients with metastatic  ER+ breast cancer also receive hormone therapy as first-line  treatment. Patients with ER+/PR+ locally advanced breast cancer  including potentially operable cases (cT2N1, cT3N0M0) are still a  subject to neoadjuvant chemotherapy in most of the oncology  centers in Russia and worldwide. More than 10 years ago, several  trials evaluating the efficacy of neoadjuvant endocrine therapy were  conducted in the Petrov Research Institute of Oncology (aromatase  inhibitors vs tamoxifen, neoadjuvant endocrine therapy vs  neoadjuvant chemotherapy, etc.) The primary endpoint was the  evaluation of pathologic complete/partial response to therapy and  the frequency of breast-conserving surgeries following neoadjuvant  treatment. We now represent 10-year long-term follow-up data on  comparison of neoadjuvant chemotherapy with neoadjuvant  endocrine therapy after retrospective determination of IHC- phenotypes of 239 patients with ER+ breast cancer. The study  results show tendency to better 10-year disease-free survival in  patients with luminal-A breast cancer who received endocrine  therapy compared to neoadjuvant chemotherapy (72.8 % vs 53.9  %, respectively, p=0.062) There were no statistically significant  differences in DFS rates among patients with the luminal B breast  cancer subtype (41 % vs 40 %) The discovery of biomarkers of  potential resistance to endocrine therapy (cycline-dependant kinase  activity [cdk 4/6], estrogenreceptor mutation [ESR1], mTOR  signaling pathway activity, co-expression of the ER and HER2neu  [ER+/ HER2neu3+]) and ways to inhibit the activity of the resistance pathways (palbocyclib, everolimus, etc.) have expanded the  armamentarium of endocrine-therapy for not only metastatic and  locally-advanced but also operable cases of ER+ breast cancer.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11098-11098
Author(s):  
D. Gschwantler-Kaulich ◽  
A. Fink-Retter ◽  
T. Bachrich ◽  
M. Ledesma ◽  
E. Ruecklinger ◽  
...  

11098 Background: Neoadjuvant chemotherapy is the treatment of choice for locally-advanced breast cancer and leads to down staging and improved BCT rates. While its efficacy is well established, considerably less is known about the most effective regimen. Methods: We have performed a retrospective analysis of 132 breast cancer patients who had undergone neoadjuvant chemotherapy at our institution. Patients had either received a) anthracyclines (“A”, n=35), b) anthracyclines and taxanes (“AT”, n=55), or c) neither of the two compounds (“NoA/T”, n=42). Clinical response, pathological response and survival were evaluated in each arm. Results: While all three regimen resulted in significant tumor regression, AT was most effective with a mean tumor shrinkage of 39% (ultrasound) and 41% (mammography) (Kruskal-Wallis, p=0.004, and p=0.027). Breast conservation was achieved in 75% by AT, in 49% by A, and in 19% by NoA/T (Kruskal-Wallis, p<0.001). The treatment groups did not differ in respect to pCR (χ2-test, p=0.068), although higher cumulative anthracycline doses were predictive of pCR in multivariate analyses (p=0.022). While the mammographic and not the ultrasound-determined tumor diameter determined whether a woman underwent BCT, only an ultrasound-determined size reduction was predictive for DFS and OS (log rank, p=0.0093, and p=0.044, respectively). Other parameters that affected BCT rates were age (p= 0.003), year of diagnosis (p=<0.001), presence of multifocal disease (p= 0.032) and the cumulative anthracycline dose (p= <0.001). Conclusions: While the combination of anthracyclines and taxanes is most effective in achieving clinical remission and BCT, the cumulative anthracycline dose appears most important for achieving pCR. No significant financial relationships to disclose.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 135-135
Author(s):  
F. Marziona ◽  
A. Mattar ◽  
R. Hegg ◽  
S. J. Belloni ◽  
S. B. Rocha ◽  
...  

135 Background: Endocrine therapy is a well-established treatment for hormone-positive breast cancer, both in the adjuvant and the metastatic setting. Neoadjuvant chemotherapy has been used to increase the number of patients who are eligible for breast-conservation therapy (BCT) by inducing tumor downstaging. Neoadjuvant endocrine therapy (NET) is mostly used in patients who are not eligible for chemotherapy (almost reserved to postmenopausal patients). The clinical response with NET in postmenopausal patients with locally advanced breast cancer (LABC) and positive hormonal receptors is almost 75% with aromatase inhibitors (AI). The comparison among tamoxifen and the three AI (anastrozole, letrozole, and exemestane) shows a superiority to AI regarding BCT. There are few data in premenopausal women and NET. Methods: 29 women with rich positive hormone receptor were enrolled in the study between January to September of 2010. Patients received exemestane 25mg/day (EXE) and as we included both pre (12 patients) and postmenopausal (17 patients) women, the premenopausal ones were submitted to ooforectomy. Results: All patients were clinical stage III. In the premenopausal group 6 patients were submitted to surgery and 5 are still taking EXE. Between the two groups 9 patients were submitted to surgery, 4 showed response and are scheduling to surgery, 10 are still taking exemestane. Five patients had serious comorbidities and were submitted to radiotherapy after 9 months of EXE (one without clinical tumor) and are asymptomatic for at least 4 months. Just one patient (premenopausal) had tumor progression after 5 months of EXE and was switched to chemotherapy. Most common side effects were arthralgia/myalgia grade 1/2. Conclusions: In Brazil LABC is frequent and neoadjuvant chemotherapy is the standard treatment. We offered a treatment with a lower cost and especially lower side effects. Because of the initial stage, BCS was not possible, but we had clinical response in about 75% of the patients. This approach was good for patients with comorbidities, and despite the NET is not established for premenopausal patients our initial results encourage us to recommend it.


2011 ◽  
Vol 77 (7) ◽  
pp. 850-855 ◽  
Author(s):  
Raeshell S. Sweeting ◽  
Nancy Klauber-Demore ◽  
Michael O. Meyers ◽  
Allison M. Deal ◽  
Emily M. Burrows ◽  
...  

Women with locally advanced breast cancer (LABC) who are breast conservation (BCT) candidates after neoadjuvant chemotherapy have the best long-term outcome and low local-regional recurrence (LRR) rates. However, young women are thought to have a higher risk of LRR based on historical data. This study sought to evaluate LRR rates in young women who undergo BCT after neoadjuvant chemotherapy. We identified 122 women aged 45 years or younger with American Joint Committee on Cancer (AJCC) Stage II to III breast cancer, excluding T4d, treated with neoadjuvant chemotherapy from 1991 to 2007 from a prospective, Institutional Review Board-approved, single-institution database. Data were analyzed using Fisher eExact test, Wilcoxon tests, and the Kaplan-Meier method. Median follow-up was 6.4 years. Fifty-four (44%) patients had BCT and 68 (56%) mastectomy. Forty-six per cent were estrogen receptor-positivity and 28 per cent overexpressed Her2. Mean pretreatment T size was 5.6 cm in the BCT group and 6.7 cm in the mastectomy group ( P = 0.04). LRR rates were no different after BCT compared with mastectomy (13 vs 18%, P = 0.6). Higher posttreatment N stage ( P < 0.001) and AJCC stage ( P = 0.008) were associated with LRR but not pretreatment staging. Disease-free survival was better for patients achieving BCT, with 5-year disease-free survival rates of 82 per cent (95% CI, 69 to 90%) compared with 58 per cent (95% CI, 45 to 69%) for mastectomy ( P = 0.03). Young women with LABC who undergo BCT after neoadjuvant chemotherapy appear to have similar LRR rates compared with those with mastectomy. This suggests that neoadjuvant chemotherapy may identify young women for whom BCT may have an acceptable risk of LRR.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252822
Author(s):  
Takayuki Watanabe ◽  
Takaaki Oba ◽  
Keiji Tanimoto ◽  
Tomohiro Shibata ◽  
Shinobu Kamijo ◽  
...  

Sequential treatment with endocrine or chemotherapy is generally used in the treatment of estrogen receptor (ER)-positive recurrent breast cancer. To date, few studies have investigated the effect of long-term endocrine therapy on the response to subsequent chemotherapy in ER-positive breast cancer. We examined whether a preceding endocrine therapy affects the sensitivity to subsequent chemotherapy in ER-positive breast cancer cells. Three ER-positive breast cancer cell lines (T47D, MCF7, BT474) and tamoxifen-resistant sublines (T47D/T, MCF7/T, BT474/T) were analyzed for sensitivity to 5-fluorouracil, paclitaxel, and doxorubicin. The mRNA levels of factors related to drug sensitivity were analyzed by RT-PCR. MCF7/T cells became more sensitive to 5-fluorouracil than wild-type (wt)-MCF7 cells. In addition, the apoptosis induced by 5-fluorouracil was significantly increased in MCF7/T cells. However, no difference in sensitivity to chemotherapeutic agents was observed in T47D/T and BT474/T cells compared with their wt cells. Dihydropyrimidine dehydrogenase (DPYD) mRNA expression was significantly decreased in MCF7/T cells compared with wt-MCF7 cells. The expression of DPYD mRNA was restored with 5-azacytidine treatment in MCF7/T cells. In addition, DPYD 3′-UTR luciferase activity was significantly reduced in MCF7/T cells. These data indicated that the expression of DPYD mRNA was repressed by methylation of the DPYD promoter region and post-transcriptional regulation by miRNA in MCF7/T cells. In the mouse xenograft model, capecitabine significantly reduced the tumor volume in MCF7/T compared with MCF7. The results of this study indicate that endocrine therapy could alter the sensitivity to chemotherapeutic agents in a subset of breast cancers, and 5-fluorouracil may be effective in tamoxifen-resistant breast cancers.


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