scholarly journals IHC-based Ki67 as response biomarker to tamoxifen in breast cancer window trials enrolling premenopausal women

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stacey E. P. Joosten ◽  
Marius Wellenstein ◽  
Rutger Koornstra ◽  
Annelot van Rossum ◽  
Joyce Sanders ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Postmenopausal Breast Cancer ◽  
Premenopausal Women ◽  
Blood Levels ◽  
Breast Cancer Patients ◽  
Premenopausal Breast Cancer ◽  
Estradiol Levels

AbstractWindow studies are gaining traction to assess (molecular) changes in short timeframes. Decreased tumor cell positivity for the proliferation marker Ki67 is often used as a proxy for treatment response. Immunohistochemistry (IHC)-based Ki67 on tissue from neo-adjuvant trials was previously reported to be predictive for long-term response to endocrine therapy for breast cancer in postmenopausal women, but none of these trials enrolled premenopausal women. Nonetheless, the marker is being used on this subpopulation. We compared pathologist assessed IHC-based Ki67 in samples from pre- and postmenopausal women in a neo-adjuvant, endocrine therapy focused trial (NCT00738777), randomized between tamoxifen, anastrozole, or fulvestrant. These results were compared with (1) IHC-based Ki67 scoring by AI, (2) mitotic figures, (3) mRNA-based Ki67, (4) five independent gene expression signatures capturing proliferation, and (5) blood levels for tamoxifen and its metabolites as well as estradiol. Upon tamoxifen, IHC-based Ki67 levels were decreased in both pre- and postmenopausal breast cancer patients, which was confirmed using mRNA-based cell proliferation markers. The magnitude of decrease of Ki67 IHC was smaller in pre- versus postmenopausal women. We found a direct relationship between post-treatment estradiol levels and the magnitude of the Ki67 decrease in tumors. These data suggest IHC-based Ki67 may be an appropriate biomarker for tamoxifen response in premenopausal breast cancer patients, but anti-proliferative effect size depends on estradiol levels.

scholarly journals Need for Weight Management among Postmenopausal Early Breast Cancer Patients Receiving Adjuvant Endocrine Therapy

2005 ◽  
Vol 1 (2) ◽  
pp. 205-222 ◽  
Author(s):  
Michelle Harvie ◽  
Tony Howell
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Cancer Patients ◽  
Weight Management ◽  
Endocrine Therapy ◽  
Breast Cancer Survivors ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancer Patients ◽  
Mortality And Morbidity ◽  
The Impact

Increasingly effective adjuvant therapies mean that the prognosis for postmenopausal women with breast cancer has never been better. Weight problems are common among breast cancer patients and worsen due to the impact of diagnosis and treatment. Recent studies have linked excess weight with the risk of recurrence of breast cancer among premenopausal women. While general obesity (body mass index) does not appear to influence the already much improved prognosis for postmenopausal women, there is some evidence that limiting central obesity and improving insulin resistance may improve survival. The focus of attention for postmenopausal breast cancer survivors is also shifting to consider the mortality and morbidity from other weight-related cancers and noncancer causes, such as cardiovascular disease, making weight control a potentially important adjunct to endocrine therapy. This paper outlines the rationale and optimal design for effective weight management strategies among postmenopausal breast cancer patients receiving endocrine therapy.

scholarly journals Validation of the Clinical Treatment Score Post–Five Years in Breast Cancer Patients for Predicting Late Distant Recurrence: A Single-Center Investigation in Korea

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun-Hee Lee ◽  
Se Kyung Lee ◽  
Byung Joo Chae ◽  
Jonghan Yu ◽  
Jeong Eon Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Distant Metastasis ◽  
Premenopausal Women ◽  
Distant Recurrence ◽  
Breast Cancer Patients ◽  
Risk Of Recurrence ◽  
Positive Breast Cancer

BackgroundEndocrine therapy is administered to hormone-positive breast cancer patients to prevent distant metastasis. It is important to evaluate the risk of recurrence and to determine which patients are viable candidates for such treatment because hormone therapy has side effects that can include postmenopausal symptoms. The Clinical Treatment Score post–five years (CTS5), a simple tool for identifying candidates for endocrine therapy, was recently introduced; however, CTS5 only has been applied in validation studies with postmenopausal women. We aimed to validate CTS5 among premenopausal breast cancer patients.MethodsWe identified patients treated between 1994 and 2014 at Samsung Medical Center in Seoul, Korea, and followed their treatment outcomes for more than 60 months after surgery using clinicopathologic parameters. According to menopausal status, we divided the study population into two groups: pre- and postmenopausal women. After calculating CTS5 values based on some parameters, we stratified the rate of late distant recurrence (DR) and analyzed the correlation between CTS5 value and late DR by risk.ResultsAmong 16,904 patients treated surgically for breast cancer, 2,605 with hormone receptor–positive breast cancer who received endocrine therapy were included. Of these, 1,749 (67.14%) patients were premenopausal women, and the median age was 44.00 years. When categorizing study participants according to CTS5-related risk for late DR, 86.79% were categorized as low risk, 5.95% were categorized as intermediate risk, and 7.26% were categorized as high risk. The annual rate of DR was 1.41% for those in the present study and was similar between pre- and postmenopausal participants (1.40 vs. 1.42). Distant metastasis-free survival was not different between the two groups (hazard ratio: 0.817, 95% confidence interval [CI]: 0.547–1.221). The area under the receiver operating characteristic curve at 10 years for premenopausal and postmenopausal patients was 61.75 (95% CI: 52.97–70.53) and 72.71 (95% CIs: 63.30–82.12), respectively.ConclusionsAlthough CTS5 was able to predict late DR, it should be applied with caution in premenopausal women. A CTS5 calculator for premenopausal women might be needed to not underestimate the risk of recurrence in Korea.

scholarly journals Comprehensive profiles and diagnostic value of menopausal-specific gut microbiota in premenopausal breast cancer

2021 ◽  
Author(s):  
Ming-Feng Hou ◽  
Fu Ou-Yang ◽  
Chung-Liang Li ◽  
Fang-Ming Chen ◽  
Chieh-Han Chuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gut Microbiota ◽  
Cancer Patients ◽  
Critical Role ◽  
Postmenopausal Breast Cancer ◽  
Diagnostic Value ◽  
Breast Cancer Patients ◽  
Premenopausal Breast Cancer ◽  
Α Diversity ◽  
Functional Pathways

AbstractIn Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.

A validated model to predict low recurrence risk distinguished by 21-gene recurrence score in hormone receptor-positive invasive breast cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 532-532
Author(s):  
Yasue Tsuchida ◽  
Sachiko Ohde ◽  
Ryota Nakamura ◽  
Yoko Kanada ◽  
Sakiko Miura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Prediction Model ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Recurrence Score ◽  
Premenopausal Women ◽  
Breast Cancer Patients ◽  
Derivation Cohort

532 Background: In the prospective TAILORx and RxPONDER trials, the 21-gene Recurrence Score (RS) showed endocrine therapy alone was non-inferior to chemo-endocrine therapy in the analysis of invasive disease-free survival in postmenopausal hormone-receptor (HR)-positive breast cancer patients with RS < = 25. They also indicated chemotherapy was associated with benefit for women 50 years or younger with RS 11 to 25. However, in Japan, the test is not conventionally available because of non-coverage by national insurance. We aimed to develop and validate a model to predict RS using clinicopathological factors that identify patients who would have low risk shown by testing the 21-gene RS and can avoid chemotherapy. Methods: Four hundred patients, including 187 N0/1 postmenopausal, and 213 N0 premenopausal women who underwent surgery and had the RS from St. Luke’s International Hospital, Tokyo, Japan, were included in derivation cohort. Derivation cohort was divided into 2 groups by RS 25; patients with RS of 0 to 25 (n = 321) and with RS over 26 (n = 79). Multivariate logistic regression analysis was performed using candidate factors for all patients and pre- or postmenopausal patients. The prediction model was validated using an external cohort of 70 patients from Showa University School of Medicine, Tokyo, Japan. Results: Nuclear grade (NG) (adjusted OR, 5.28, 95% CI, 2.47–11.30), high Progesterone receptor (PgR) expression (Allred score 7-8) (adjusted OR, 10.62, 95% CI, 5.34–21.13) and low Ki67 level ( < = 20%) (adjusted OR, 5.29, 95% CI, 2.33-12.01) were significant independent predictors of RS of 0 to 25. With these factors could predict RS of 0 to 25 (AUC of 0.848, 95% CI, 0.803-0.893) with the highest probability of low-RS for 100%. The prediction model of the validation cohort had same discriminatory ability having an AUC of 0.812 (95% CI, 0.701-0.923). In postmenopausal patients, NG (adjusted OR, 4.81, 95% CI, 1.72–13.42), high PgR expression (adjusted OR, 10.62, 95% CI, 4.52–37.72), and low Ki67 level (adjusted OR, 4.94, 95%CI, 1.87-13.04) were significantly associated with RS of 0 to 25 in multivariate analysis. A regression model with these 4 factors could predict RS of 0 to 25 (AUC of 0.842, 95%CI, 0.782-0.902). In premenopausal patients, NG (adjusted OR, 8.76, 95% CI, 1.14–67.40), high PgR expression (adjusted OR, 3.22, 95% CI, 1.61–6.43), and low Ki67 level (adjusted OR, 2.87, 95% CI, 1.20–6.87) were significantly associated with RS of 0 to 10 in multivariate analysis. These factors could predict RS of 0 to 10 (AUC of 0.811, 95% CI, 0.731-0.891). However, the highest probability of low-RS provided this model for premenopausal women was 46.8%. Conclusions: Our validated model could provide useful information to distinguish low-RS especially for postmenopausal patients with high reproducibility. However, for premenopausal women, the 21-gene RS is warranted.

Association of the phosphorylation of the estrogen receptor at serine 118 and 167 with prognosis in postmenopausal breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 562-562
Author(s):  
Karin J. Beelen ◽  
Mark Opdam ◽  
Rutger H.T. Koornstra ◽  
Andrew D. Vincent ◽  
Jan Baptist Vermorken ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Estrogen Therapy ◽  
Postmenopausal Breast Cancer ◽  
Tamoxifen Treatment ◽  
Adjuvant Tamoxifen ◽  
Breast Cancer Patients ◽  
Premenopausal Breast Cancer ◽  
Cox Models

562 Background: The sensitivity of the estrogen receptor (ERα) to anti-estrogen therapy can be affected by phosphorylation events. In premenopausal breast cancer patients, phosphorylation of the ERα at serine 118 (ERαS118-p) is predictive for benefit from adjuvant tamoxifen. Since ERαS118-p represents the common hallmark of different signaling cascades that differ in E2 dependency, the resulting effect on estrogen sensitivity may differ between pre- and postmenopausal patients. Phosphorylation of serine 167 (ERαS167-p) has been associated with favorable disease outcome, but whether ERαS167-p can predict tamoxifen sensitivity is currently unknown. We tested the predictive value of both ERαS118-p and ERαS167-p for benefit from adjuvant tamoxifen in postmenopausal breast cancer patients. Methods: We collected primary tumor blocks from 563 ERα positive (stage I-III) postmenopausal patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (IKA trial). The median follow-up of patients without a recurrence event was 9.4 years. Immunohistochemistry was performed on a TMA using monoclonal antibodies for ERαS118-p and ERαS167-p. The percentage of positive nuclei was scored and a score of ≥ 10 % was considered as positive. Multivariate Cox models were used to assess hazard ratios (HRs) for recurrence free interval and the interaction between these phosphorylations and tamoxifen treatment. Results: We did not find a significant interaction between either ERαS118-p (p=0.99) or ERαS167-p (p=0.44) and tamoxifen, suggesting that the relative benefit from adjuvant tamoxifen in postmenopausal patients is not dependent on the presence of one of these phosphorylations. Both tamoxifen treated patients as well as control patients had a better prognosis when their tumor was positive for ERαS118-p (adjusted HR 0.60 p=0.02) or ERαS167-p (adjusted HR 0.62, p=0.02) compared to patients whose tumor did not express these ERα phosphorylations. Conclusions: In postmenopausal patients ERαS118-p and ERαS167-p are both associated with better prognosis, but do not predict differential benefit from tamoxifen.

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