Machine learning-based prediction of breast cancer growth rate in-vivo

BackgroundDetermining the rate of breast cancer (BC) growth in vivo, which can predict prognosis, has remained elusive despite its relevance for treatment, screening recommendations and medicolegal practice. We developed a model that predicts the rate of in vivo tumour growth using a unique study cohort of BC patients who had two serial mammograms wherein the tumour, visible in the diagnostic mammogram, was missed in the first screen.MethodsA serial mammography-derived in vivo growth rate (SM-INVIGOR) index was developed using tumour volumes from two serial mammograms and time interval between measurements. We then developed a machine learning-based surrogate model called Surr-INVIGOR using routinely assessed biomarkers to predict in vivo rate of tumour growth and extend the utility of this approach to a larger patient population. Surr-INVIGOR was validated using an independent cohort.ResultsSM-INVIGOR stratified discovery cohort patients into fast-growing versus slow-growing tumour subgroups, wherein patients with fast-growing tumours experienced poorer BC-specific survival. Our clinically relevant Surr-INVIGOR stratified tumours in the discovery cohort and was concordant with SM-INVIGOR. In the validation cohort, Surr-INVIGOR uncovered significant survival differences between patients with fast-growing and slow-growing tumours.ConclusionOur Surr-INVIGOR model predicts in vivo BC growth rate during the pre-diagnostic stage and offers several useful applications

Assessment of Tumor Vascularization: Immunohistochemical and Non-Invasive Methods

Growth of solid tumors beyond a certain mass is dependent on the vascular bed from pre-existing host vasculature. The process of angiogenesis is essential not only for primary tumor growth but also for metastasis. The number of microvessels within the invasive component of a primary tumor reflects the degree of tumor angiogenesis. At present the most widely used method to assess neovascularization is the quantitation of intratumoral microvessel density (IMD) by immunohistochemical methods in which specific markers for endothelial cells are employed. In this paper we analyze the different methods used to assess IMD, as well as their advantages and potential methodological pitfalls. Several studies have shown a close correlation between IMD, tumor growth and the occurrence of metastasis, suggesting that IMD is a prognostic indicator of clinical relevance. Furthermore, preliminary studies suggest that determination of angiogenesis may predict responsiveness to some forms of conventional anticancer therapy. Although the histological microvessel density technique is the current gold standard to characterize tumor angiogenesis, it may not be the ideal tool for clinical purposes because it needs to be performed on biopsy material and does not assess the functional pathways involved in the angiogenic activity of tumors. Non-invasive assessment of tumor vascularity is possible in vivo by means of Doppler sonography, dynamic contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography (PET). These methods may be preferable to histological assay because they are non-invasive, survey the entire tumor, reflect both anatomic and physiologic characteristics, and may be useful to monitor the activity of antiangiogenic therapies. </jats:p

The role of letrozole (FEMARA®) in breast cancer therapy: A clinical review

Letrozole is a third-generation aromatase inhibitor for use in postmenopausal women with hormonal-sensitive breast cancer. This drug was found to reduce or effectively shrink tumors in a significant number of such patients. It exhibits antitumor activity at a relatively low daily dose, and is highly potent and selective and well tolerated. Results from recent phase III clinical studies have confirmed the efficacy and the key role of this drug in the therapy of advanced breast cancer in postmenopausal women. Moreover, letrozole demonstrated higher activity and lower toxicity compared to tamoxifen in the first-line therapy of postmenopausal women affected with advanced breast cancer. However, it also represents a valid option in second-line therapy after tamoxifen failure. New data on this agent in adjuvant or neoadjuvant treatment also suggest efficacy in the treatment of early breast cancer. This article reviews the clinical data on letrozole in all settings and its future potential in chemoprevention. (C) 2001 Prous Science. All rights reserved

Behaviour of metastasis in relation to vascular index in patients with node-positive breast cancer treated with adjuvant tamoxifen

Some experimental studies suggested that one possible oestrogen-receptor-unrelated mechanism of action of tamoxifen involves inhibition of angiogenesis. We evaluated the correlation of the degree of vascularisation of the primary tumour and we assessed it by using the panendothelial marker anti-CD31 and immunohistochemistry with microvessels count, performed at the vascular 'hot spot' of each single cancer, with the risk of recurrence in time. A cohort of 176 consecutive patients with node-positive invasive breast cancer treated with adjuvant tamoxifen (30 mg/daily for 3 years) and a median follow-up of 72 months was studied. Sixty-two patients developed metastasis (30 visceral, 18 skeletal and 14 in soft tissues) during the time of observation. The study of the hazard function for metastasis was performed by a generalized linear modelling approach with a binomial error according to Efron. The risk of first recurrence was strictly associated with vascular index, having the patients with the highest microvessel counts the highest risk of metastasis during all the period of observation. We did not find an interaction of vascularity with oestrogen receptor (ER) status. However, in the subgroup of patients with ER-positive tumours the hazard of metastasis was almost constant in time, while in that with ER-negative tumours it increased rapidly up to 20 months and, thereafter, decreased sharply. The results of our study are an indirect evidence that the patients with highly vascularized breast cancers may gain poor benefit of adjuvant tamoxifen and, therefore. that this antioestrogen is unlikely to retain a clinically relevant antiangiogenic activity in human breast cancer. Our data need confirmation by a prospective randomized clinical trial

Rationale for the use of gemcitabine in breast cancer (Review)

Many active cytotoxic drugs and several regimens exist for breast cancer therapy. However, these conventional treatments have not changed the outcome of patients with locally advanced and metastatic disease. As a consequence, the dynamic balance between chemotherapy-induced side effects and benefits attributable to relief of cancer-related symptoms must be carefully considered in this setting. Gemcitabine is a pyrimidine nucleoside antimetabolite that has shown activity in a variety of solid tumors, a good toxicity profile, and non-overlapping toxicity with other chemotherapeutic drugs. As a single agent, gemcitabine yields response rates ranging from 14 to 37% as first-line treatment for advanced breast cancer and 12-30% as salvage therapy for patients previously treated with anthracycline and/or taxane treatment. Combined with vinorelbine, platinum, anthracyclines, and taxanes as doublets or triplets, response rates of 50 to 80% have been reported in phase II clinical studies. Gemcitabine in combination with anthracyclines and taxanes has been evaluated in the neoadjuvant setting in patients with early-stage breast cancer with interesting clinical and pathological response rates. Preliminary results of gemcitabine in combination with the biologic agent, trastuzumab, are encouraging. Phase III trials of gemcitabine combinations compared to standard regimens are ongoing with the aim to assess the independent contribution of gemcitabine

Current status and future potential role of exemestane in the treatment of early and advanced breast cancer (Review)

Exemestane is a new oral steroidal aromatase inactivator, active in postmenopausal women with hormonal sensitive breast carcinoma. This drug, at a dosage of 25 mg once daily, was shown to suppress in vivo aromatase activity by 97.9%, with a subsequent reduction superior to 85% of circulating oestrogen level. It exhibits definite antitumor activity at a relatively low daily dose, and is highly potent, highly selective, and well-tolerated. Moreover, for postmenopausal women with metastatic breast cancer, exemestane demonstrated a higher activity and lower toxicity profile when compared to megestrol acetate and tamoxifen in second- and first-line therapy, respectively. New data on exemestane are forthcoming both in the adjuvant and neoadjuvant setting, which could improve the management of early breast cancer in the future