The Impact of Exogenous Estrogen Exposure on the Characteristics and Outcome of Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early-Stage Breast Cancer

Oncology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Orly Yariv ◽  
Raz Mutai ◽  
Ofer Rotem ◽  
Daliah Tsoref ◽  
Yasmin Korzets ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Fertility Treatments ◽  
Estrogen Exposure ◽  
Exogenous Estrogen ◽  
Er Positive ◽  
Epidermal Growth ◽  
The Impact

<b><i>Introduction:</i></b> The impact of exogenous estrogen exposure on breast cancer characteristics and outcomes is not well described. We aimed to investigate the effect of prior treatment with oral contraceptives (OCT), hormone replacement therapy (HRT), and fertility treatments on early-stage, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. <b><i>Methods:</i></b> This is a single-center retrospective cohort study comprising all women with ER-positive, HER2-negative, early breast cancer whose tumors were sent to Oncotype DX analysis between 2005 and 2012. Data on prior exposures to OCT, HRT, and fertility treatments were collected. The impact of these exposures on prespecified histopathological features was assessed including tumor size, nodal status, intensity of the hormonal receptors, grade, Oncotype recurrence score, Ki67, and lymphovascular and perineural invasion. The impact of these exposures on disease-free survival (DFS) and overall survival (OS) was also evaluated. <b><i>Results:</i></b> A total of 620 women were included, of which 19% had prior exposure to OCT, 30% to HRT, and 11% to fertility treatments. OCT use was associated with smaller (≤1 cm) tumors (<i>p</i> = 0.023) and were less likely to have grade 3 disease (<i>p</i> = 0.049). No other associations were found between exogenous estrogen exposure and tumor characteristics. Median follow-up was 10.4 years. Ten-year DFS was 85.7%, and it was not influenced by exogenous exposure. Ten-year OS was 90.2%, and OCT was associated with improved OS in univariate analysis (HR = 0.31, 95% CI: 0.11–0.85), but this difference did not remain significant in multivariate analysis (<i>p</i> = 0.275). <b><i>Conclusion:</i></b> The impact of exogenous estrogen exposure on ER-positive, HER2-negative early breast cancer characteristics is limited. In the long term, none of the evaluated exposures had negative effect on DFS and OS.

The impact of exogenous estrogen exposure on the characteristics of estrogen receptor (ER) positive, early-stage breast cancer (EBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12606-e12606
Author(s):  
Orly Yariv ◽  
Rinat Yerushalmi ◽  
Assaf Moore ◽  
Tzippy Shohat ◽  
Ofer Rotem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Hormone Replacement ◽  
Luminal Breast Cancer ◽  
Fertility Treatments ◽  
Estrogen Exposure ◽  
Exogenous Estrogen ◽  
Er Positive ◽  
The Impact

e12606 Background: Oral contraceptives (OC) and hormone replacement therapy (HRT) are well-established risk factors for ER positive breast cancer. Infertility is associated with an increased breast cancer risk and there is conflicting data on the influence of fertility treatments on breast cancer risk. The impact of exogenous estrogen exposure on breast cancer characteristics is not well described. Methods: A single center retrospective cohort study comprising all women with ER positive, human epidermal growth factor receptor 2 (HER2) negative, EBC whose tumors were sent to OncotypeDX analysis treated in our institute between 2005 and 2012. Data on exogenous estrogen exposure were collected including: OC and HRT use and prior fertility treatments. The impact of these exposures was assessed on pre-specified histopathological features including: tumor size, nodal status, ER and progesterone receptor (PR) staining, grade, Oncotype recurrence score (RS), ki67, lymphovascular and perineural invasion. Results: A total of 620 women were included, 79% were postmenopausal. Prior exposure to OC, HRT and fertility treatments was documented in 19% (103), 30% (136) and 11% (62), respectively. OC use was associated with smaller (≤1cm) tumors (30% vs. 20%, p = 0.023) and were less likely to have grade 3 disease (10% vs. 19%, p = 0.049). No other associations were found between exogenous estrogen exposures and tumor characteristics (Table). Conclusions: Use of OC may be associated with breast cancer with a distinct features compared to women with luminal breast cancer without history of OC use. Large scale studies are needed to better characterize these findings. [Table: see text]

Automated NLP Extraction of Clinical Rationale for Treatment Discontinuation in Breast Cancer

2021 ◽  
pp. 550-560
Author(s):  
Matthew S. Alkaitis ◽  
Monica N. Agrawal ◽  
Gregory J. Riely ◽  
Pedram Razavi ◽  
David Sontag
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Logistic Regression ◽  
Standard Deviation ◽  
Early Stage ◽  
Area Under The Curve ◽  
Growth Factor Receptor ◽  
Treatment Discontinuation ◽  
High Dimensional ◽  
Epidermal Growth

PURPOSE Key oncology end points are not routinely encoded into electronic medical records (EMRs). We assessed whether natural language processing (NLP) can abstract treatment discontinuation rationale from unstructured EMR notes to estimate toxicity incidence and progression-free survival (PFS). METHODS We constructed a retrospective cohort of 6,115 patients with early-stage and 701 patients with metastatic breast cancer initiating care at Memorial Sloan Kettering Cancer Center from 2008 to 2019. Each cohort was divided into training (70%), validation (15%), and test (15%) subsets. Human abstractors identified the clinical rationale associated with treatment discontinuation events. Concatenated EMR notes were used to train high-dimensional logistic regression and convolutional neural network models. Kaplan-Meier analyses were used to compare toxicity incidence and PFS estimated by our NLP models to estimates generated by manual labeling and time-to-treatment discontinuation (TTD). RESULTS Our best high-dimensional logistic regression models identified toxicity events in early-stage patients with an area under the curve of the receiver-operator characteristic of 0.857 ± 0.014 (standard deviation) and progression events in metastatic patients with an area under the curve of 0.752 ± 0.027 (standard deviation). NLP-extracted toxicity incidence and PFS curves were not significantly different from manually extracted curves ( P = .95 and P = .67, respectively). By contrast, TTD overestimated toxicity in early-stage patients ( P < .001) and underestimated PFS in metastatic patients ( P < .001). Additionally, we tested an extrapolation approach in which 20% of the metastatic cohort were labeled manually, and NLP algorithms were used to abstract the remaining 80%. This extrapolated outcomes approach resolved PFS differences between receptor subtypes ( P < .001 for hormone receptor+/human epidermal growth factor receptor 2− v human epidermal growth factor receptor 2+ v triple-negative) that could not be resolved with TTD. CONCLUSION NLP models are capable of abstracting treatment discontinuation rationale with minimal manual labeling.

scholarly journals Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 737 ◽  
Author(s):  
Denis M. Collins ◽  
Neil T. Conlon ◽  
Srinivasaraghavan Kannan ◽  
Chandra S. Verma ◽  
Lisa D. Eli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Epidermal Growth

An estimated 15–20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2/ERBB2/neu). Two small-molecule tyrosine kinase inhibitors (TKIs), lapatinib and neratinib, have been approved for the treatment of HER2-positive (HER2+) breast cancer. Lapatinib, a reversible epidermal growth factor receptor (EGFR/ERBB1/HER1) and HER2 TKI, is used for the treatment of advanced HER2+ breast cancer in combination with capecitabine, in combination with trastuzumab in patients with hormone receptor-negative metastatic breast cancer, and in combination with an aromatase inhibitor for the first-line treatment of HER2+ breast cancer. Neratinib, a next-generation, irreversible pan-HER TKI, is used in the US for extended adjuvant treatment of adult patients with early-stage HER2+ breast cancer following 1 year of trastuzumab. In Europe, neratinib is used in the extended adjuvant treatment of adult patients with early-stage hormone receptor-positive HER2+ breast cancer who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy. Preclinical studies have shown that these agents have distinct properties that may impact their clinical activity. This review describes the preclinical characterization of lapatinib and neratinib, with a focus on the differences between these two agents that may have implications for patient management.

scholarly journals Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

2016 ◽  
Vol 34 (10) ◽  
pp. 1134-1150 ◽  
Author(s):  
Lyndsay N. Harris ◽  
Nofisat Ismaila ◽  
Lisa M. McShane ◽  
Fabrice Andre ◽  
Deborah E. Collyar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Systemic Therapy ◽  
Clinical Utility ◽  
Literature Search ◽  
Retrospective Studies ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Adjuvant Systemic Therapy ◽  
Epidermal Growth

Purpose To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. Methods A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. Recommendations In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.

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