picking the optimal endocrine adjuvant treatment for pre menopausal women

Endocrine treatments are key component of the adjuvant strategy for pre-menopausal patients with luminal tumors. Treatment options should be based not only upon the risk of relapse and level of endocrine responsiveness, but also on co-morbidities, preferences of the patient and degree of side effects. Tamoxifen should still be considered as an appropriate endocrine therapy in a large group of premenopausal patients (e.g. lower risk patient, presence of co-morbidities, patient preference). However, the results of the SOFT and TEXT trials, evaluating the value of ovarian function suppression (OFS) as well as the role of adjuvant aromatase inhibitor (AI), raised questions about the use of tamoxifen alone in selected higher risk patient. In the SOFT study, premenopausal patients did not benefit from the addition of OFS, but for those women at sufficient risk of recurrence to deserve adjuvant chemotherapy and who maintained pre-menopausal estradiol, the addition of OFS to tamoxifen reduced the risk of recurrence. Moreover, in the TEXT trial, adjuvant treatment with exemestane plus OFS, as compared with tamoxifen plus OFS, significantly improved disease-free survival, breast cancer-free interval and distant disease-free survival, thus representing a new treatment option. Recent available information on endocrine options for younger patients with luminal tumors support the use of tailored endocrine treatments. Issues specific for younger patients related to pregnancies desire, family planning, safety, quality of life and subjective side effects should be a priority in the therapeutic algorithm

extended adjuvant chemotherapy in endocrine non responsive disease

Abstract Introduction and aims There is a biological rationale for expecting benefit from longer duration therapy in the subpopulation of patients with endocrine non-responsive disease. Such tumors have a rapid cell proliferation and are associated with a high risk of relapse despite adjuvant chemotherapy. Moreover, prolonged duration of chemotherapy may be particularly relevant for patients with triple negative disease to inhibit the growth of tumors that are not susceptible to the effects of endocrine therapies due to lack of steroid hormone receptors, or to the effects of anti-HER2 target treatment. Methods and results The question of duration of adjuvant chemotherapy for breast cancer has been directly addressed in several trials herein presented. Most of these were small and, therefore, unsuitable for detecting differences of modest magnitude in intrinsic biological subtypes. In addition, a number of trials examine regimens which differ in duration of therapy, but also in the drugs given. In these trials the effects of duration and choice of drug are inextricably confounded. However incremental chemotherapy strategies, compared with less extensive therapies, were more effective in past studies particularly in patients with endocrine non-responsive disease. Conclusions The evidence resulting from past trials indicates that conventional-dose chemotherapy for 4–6 months is an adequate option in patients whose tumors present a low or no expression of steroid hormone receptors. These tumor subtypes are part of a highly heterogeneous subgroup (e.g., basal-like, molecular apocrine, claudin-low, HER-enriched). Tailored research through international cooperation is key to solidify consensus on how to treat individual patients with endocrine non-responsive breast cancer

Neoadjuvant chemotherapy for breast cancer: any progress?

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Adjuvant therapies for special types of breast cancer

Summary Recent developments in the adjuvant treatment of breast cancer include an increasing attention to systemic therapies prescribed in homogeneous groups of patients according to the higher chance of benefit. A clear consequence of the current adjuvant treatment strategy is the importance of accurate and reliable histopathological assessment. A proper pathological evaluation may effectively support the definition of prognosis and treatment choice in niches of patients diagnosed with special types of breast cancer. Through the identification of special types of breast cancer, that account for up to 25% of all invasive breast carcinomas, it is possible to select patients with a very good prognosis often close to that of the general population (e.g. tubular and pure cribriform carcinoma). Other features, such as those related with invasive classical lobular carcinoma, might have important correlates of responsiveness to therapy other than indicators of outcome. It was in fact demonstrated that the response to primary chemotherapy is significantly lower in invasive lobular carcinoma, if compared with the ductal histotype. However, the use of available information on special types of breast cancer has been limited in tailoring adjuvant therapy, owing to the absence of standardized criteria and partial reproducibility for diagnosis. Moreover, due to the relative rarity of the disease a large number of features that identify for special types of breast carcinomas have today no particular correlation with the prognosis, and limited data are available on the biology of a large number of breast cancer subtypes. The development of more effective therapies for patients with special types of breast cancer requires tailored treatment investigations through international cooperation and should not rely on information predominantly contributed from small retrospective analyses. Examination of patterns of relapse and treatment response within subpopulations in multiple randomized trials is also mandatory to make progress and reach consensus on how to treat individual patients with special types of breast cancer

lessons on responsiveness to adjuvant systemic therapies learned from the neoadjuvant setting

Summary Aims Recommended principles for the choice of therapies in operable breast cancer include the recognition of diverse subtypes of breast cancer and, based on genetic signature and immunohistochemistry, the identification of targets and related factors predictive of response. We review recent developments in the knowledge of established predictive factors in the neo-adjuvant setting. Methods and Results Experimental and clinical studies have shown that the degree of expression of estrogen receptor (ER) and progesterone receptor (PgR) of the primary tumor defines distinct biological entities that require a differentiated approach to neoadjuvant treatment and clinical trial investigation. In particular, tumors that express high levels of both steroid hormone receptors in a majority of cells derive no or low benefit from preoperative chemotherapy, while the absence of expression of ER and PgR was significantly correlated with the probability of pathologic complete remission (pCR). It was also demonstrated that the pCR rate to primary chemotherapy is significantly lower in invasive lobular carcinoma, frequently characterized by a high expression of steroid hormone receptors, if compared with the ductal histotype. Direct or indirect measures of high cell proliferation (elevated Ki-67 labeling index and high grade) identified patients with tumors responsive to chemotherapy in the preoperative setting. These factors might therefore assist in the identification of patients who might benefit from chemotherapy, in particular those patients with endocrine responsiveness. HER2 overexpression or amplification represents a target for neoadjuvant treatment with the humanised monoclonal antibody against its extracellular domain, but is also a factor predictive of response to neoadjuvant systemic therapies. A statistically significant positive correlation between HER2 positivity and pCR rate in patients treated with neoadjuvant chemotherapy was recently shown. Conclusions Results from studies in the neoadjuvant setting indicate that the use of factors predictive of response may permit a more effective application of therapies identifying patients likely to obtain substantial benefit from treatment

The long-term welfare effects of colonial institutions : evidence from Central India

Published online: 13 October 2023In Central India, the Narmada River separates two regions that have been ruled by different types of government only during the colonial period, and for reasons independent of their initial economic development. I implement a spatial RDD on village population in the Nineteenth Century as well as in 1901, and I run the same model on proxies of welfare in 2015. My results highlight that divergence has realised where the river overlapped with the colonial border, but not in a neighbouring area where the same Narmada River separates two shores with the same type of former colonial institution. I discuss the following transmission mechanism. The treated group was directly administered by the British with more modern state tools - such as the enforcement of property rights and a transparent taxation system - that made it easier to develop private investment. The most prominent example is the mixed-capital enterprise in charge of the construction of the first trans-continental railway. Infrastructure endowment seems to be crucial for the long-term transmission of the colonial institutional characteristics to the outcomes measured in 2015, which show better average welfare outcomes, as well as higher wealth inequality in the treated group. My work provides an explanation of how the improvement in the quality of the institutions of an embryonic state may sustain the growth of the local markets it deems relevant.This article was published Open Access with the support from the EUI Library through the CRUI - Elsevier Transformative Agreement (2023-2027)

New criteria for selecting elderly patients for breast cancer adjuvant treatment studies.

Learning Objectives After completing this course, the reader will be able to: List the factors that should be considered when choosing the appropriate adjuvant treatment for an elderly women with operable breast cancer.Discuss the possible explanations that account for the underrepresentation of elderly patients in breast cancer clinical trials.Describe the clinical trials that are being specifically conducted in elderly patients with early breast cancer to evaluate different forms of adjuvant treatments. CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.co

Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy

Abstract Background High levels of tumor-infiltrating lymphocytes (TILs) in primary triple negative and HER2-positive breast cancer (BC) have been associated with an improved patients' outcome. The role of TILs in Luminal (hormone receptor positive and HER2 negative) tumors remains to be elucidated. Moreover, the association between TILs and prognosis in the metastatic setting is still unknown. Patients and methods We evaluated the relationship between TILs and time to progression (TTP) in metastatic BC patients enrolled in a prospective phase II trial of metronomic chemotherapy, that used cyclophosphamide 50 mg daily, capecitabine 500 mg thrice daily and vinorelbine 40 mg orally three times a week (VEX combination). Results Of the 108 ER + BC patients enrolled in the VEX trial, 92 (85%) had sufficient tumor tissue and were assessed for TILs in H&E stained slides. TILs were evaluated in 38 primary BC samples and 54 metastatic sites. High (≥10%) TILs levels were significantly correlated with high Ki-67 labeling index. At multivariable analysis, each 10% increase in TILs strongly predicted a worse TTP (HR: 1.27, p = 0.008). VEX trial patients, categorized by a 3 tiers system (0–4%, 5–9% and >10% TILs) showed significantly different progression free survival curves (p = 0.011). Conclusions High TILs levels are significantly associated with a worse TTP in Luminal metastatic BC patients treated by metronomic chemotherapy. Our data confirm the reliability of TILs as a biomarker in the BC metastatic setting. The putative unfavorable prognostic role of TILs in Luminal BC patients might have clinical utility if validated by further studies

High-resolution Manometry Findings in Patients After Sclerotherapy for Esophageal Varices

Background/Aims Endoscopic therapy for esophageal varices may lead to esophageal dysmotility. High-resolution manometry is probably the more adequate tool to measure esophageal motility in these patients. This study aimed to evaluate esophageal motility using high resolution manometry following eradication of esophageal varices by endoscopic sclerotherapy. Methods We studied 21 patients (11 women, age 52 [45-59] years). All patients underwent eradication of esophageal varices with endoscopic sclerotherapy and subsequent high resolution manometry. Results A significant percentage of defective lower esophageal sphincter (basal pressure 14.3 [8.0-20.0] mmHg43% hypertonic) and hypocontractility (distal esophageal amplitude 50 [31-64] mmHgproximal esophageal amplitude 40 [31-61] mmHgdistal contractile integral 617 [403-920] mmHg center dot sec center dot cm48% ineffective) was noticed. Lower sphincter basal pressure and esophageal amplitude correlated inversely with the number of sessions (P < 0.001). No manometric parameter correlated with symptoms or interval between last endoscopy and manometry. Conclusions Esophageal motility after endoscopic sclerotherapy is characterized by: (1) defective lower sphincter and (2) defective and hypotensive peristalsis. Esophageal dysmotility is associated to an increased number of endoscopic sessions, but manometric parameters do not predict symptoms.Univ Fed Sao Paulo, Escola Paulista Med, Dept Surg, Sao Paulo, BrazilUniv Chicago, Dept Surg, 5841 S Maryland Ave, Chicago, IL 60637 USAUniv Fed Sao Paulo, Escola Paulista Med, Dept Surg, Sao Paulo, BrazilWeb of Scienc

Oral chemotherapy in advanced breast cancer: expert perspectives on its role in clinical practice

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