Erratum
(Source: JNCI Monographs)
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Tags: Erratum Source Type: research

International Expert Consensus on Primary Systemic Therapy in the Management of Early Breast Cancer: Highlights of the Fifth Symposium on Primary Systemic Therapy in the Management of Operable Breast Cancer, Cremona, Italy (2013)
Expert consensus-based recommendations regarding key issues in the use of primary (or neoadjuvant) systemic treatment (PST) in patients with early breast cancer are a valuable resource for practising oncologists. PST remains a valuable therapeutic approach for the assessment of biological antitumor activity and clinical efficacy of new treatments in clinical trials. Neoadjuvant trials provide endpoints, such as pathological complete response (pCR) to treatment, that potentially translate into meaningful improvements in overall survival and disease-free survival. Neoadjuvant trials need fewer patients and are less expensive...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Amoroso, V., Generali, D., Buchholz, T., Cristofanilli, M., Pedersini, R., Curigliano, G., Daidone, M. G., Di Cosimo, S., Dowsett, M., Fox, S., Harris, A. L., Makris, A., Vassalli, L., Ravelli, A., Cappelletti, M. R., Hatzis, C., Hudis, C. A., Pedrazzoli, Tags: Article Source Type: research

Radiotherapy Issues After Neoadjuvant Chemotherapy
Radiotherapy (RT) is standard following neoadjuvant chemotherapy (NCT) and breast-conserving surgery. NCT leads to pathologic down-staging, allowing some patients to undergo breast-conserving therapy (BCT) instead of mastectomy. BCT can also be considered in select stage III patients who respond well to NCT. Clearly-negative surgical margins should be obtained in all patients undergoing BCT. RT is used selectively following NCT and mastectomy. Indications for RT have not been fully established; retrospective data and results from National Surgical Adjuvant Breast and Bowel Project B-18 and B-27 currently form the basis for...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Mak, K. S., Harris, J. R. Tags: Article Source Type: research

Neoadjuvant Window Studies of Metformin and Biomarker Development for Drugs Targeting Cancer Metabolism
There has been growing interest in the potential of the altered metabolic state typical of cancer cells as a drug target. The antidiabetes drug, metformin, is now under intense investigation as a safe method to modify cancer metabolism. Several studies have used window of opportunity in breast cancer patients before neoadjuvant chemotherapy to correlate gene expression analysis, metabolomics, immunohistochemical markers, and metabolic serum markers with those likely to benefit. We review the role metabolite measurement, functional imaging and gene sequencing analysis play in elucidating the effects of metabolically targete...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Lord, S. R., Patel, N., Liu, D., Fenwick, J., Gleeson, F., Buffa, F., Harris, A. L. Tags: Article Source Type: research

RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy
Conclusions: RDA is a novel intermediate endpoint that has promise for clinical utility for breast cancers early in response-guided primary systemic therapy. (Source: JNCI Monographs)
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Pritzker, K., Pritzker, L., Generali, D., Bottini, A., Cappelletti, M. R., Guo, B., Parissenti, A., Trudeau, M. Tags: Article Source Type: research

High-Dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplantation for High-Risk Primary Breast Cancer
Conclusions: The administration of higher doses of chemotherapy with stem cell support may still represent a therapeutic option (and not a recommendation) in selected BC patients. This approach should be investigated further. (Source: JNCI Monographs)
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Pedrazzoli, P., Martino, M., Delfanti, S., Generali, D., Rosti, G., Bregni, M., Lanza, F., on behalf of the European Group for Blood and Marrow Transplantation (EBMT), Solid Tumor Working Party Tags: Article Source Type: research

Chemotherapy and Cognitive Function in Breast Cancer Patients: The So-Called Chemo Brain
Self-perceived problems of cognitive functioning after treatment for early-stage breast cancer have the potential to substantially affect the lives of patients. In the past two decades, neuropsychological studies have accumulated evidence of corresponding cognitive deficits that have mostly been attributed to neurotoxic effects of chemotherapy. Nevertheless, observations of impaired cognitive functioning already before the start of adjuvant or neoadjuvant chemotherapy question the singular role of chemotherapy for the causation of these deficits. The divergence between mostly subtle neuropsychological deficits and often dr...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Hermelink, K. Tags: Article Source Type: research

Effect of Primary Letrozole Treatment on Tumor Expression of mTOR and HIF-1{alpha} and Relation to Clinical Response
Conclusions: In this neoadjuvant population, LET was able to modulate the phospho-mTOR and HIF-1α pathways and may define a subpopulation of nonresponders who may be most likely to benefit from mTOR inhibitors. (Source: JNCI Monographs)
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Generali, D., Berruti, A., Cappelletti, M. R., Zanotti, L., Brugnoli, G., Forti, M., Bedussi, F., Vailati, M. E., Milani, M., Strina, C., Ardine, M., Aguggini, S., Allevi, G., Ferrero, G., Bertoni, R., Bottini, A., Harris, A. L., Fox, S. B. Tags: Article Source Type: research

Circulating Biomarkers for Prediction of Treatment Response
For cancer management, predicting and monitoring response to treatment and disease progression longitudinally is crucial due to changes in tumor biology and therapy responsiveness over time. However, solid tumors are usually sampled only at time of initial diagnosis, as obtaining tissue biopsies is an invasive procedures with associated risks. Thus, there is a pressing need for approaches able to serially detect function-related reliable biomarkers reflecting treatment response and/or disease progression through easy noninvasive procedures, amenable for longitudinal analysis of tumor molecular features. Recent evidences in...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Cappelletti, V., Appierto, V., Tiberio, P., Fina, E., Callari, M., Daidone, M. G. Tags: Article Source Type: research

IBC as a Rapidly Spreading Systemic Disease: Clinical and Targeted Approaches Using the Neoadjuvant Model
Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, younger age of onset as compared with other cancers, local and distant metastases, and lower overall survival. The multidisciplinary management of IBC includes neoadjuvant systemic chemotherapy, surgery, radiotherapy, and hormonal therapy in hormone receptor–positive disease. Pathological complete response represents an important prognostic factor suggesting IBC as the ideal in-vivo model for therapeutic development. Molecular subtyping demo...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Dawood, S., Cristofanilli, M. Tags: Article Source Type: research

Neoadjuvant Model for Testing Emerging Targeted Therapies in Breast Cancer
Neoadjuvant trials provide endpoints, such as pathological complete response (pCR) to treatment, that will potentially translate into meaningful improvements in overall survival and disease-free survival. Neoadjuvant trials need smaller sample sizes and are less expensive, and the endpoint of pCR is achieved in months, rather than years. For these reasons, the neoadjuvant setting is ideal for testing emerging targeted therapies in early breast cancer. Recently the US Food and Drug Administration has released a draft Guidance to Industry, outlining a pathway to accelerated approval for neoadjuvant breast cancer therapies us...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Esposito, A., Criscitiello, C., Curigliano, G. Tags: Article Source Type: research

The Perfect Pathology Report After Neoadjuvant Therapy
Neoadjuvant therapy is increasingly being used in the management of breast cancer patients and, since comprehensive specimen handling and precise histological reporting is essential to assess the degree of response to therapy, histopathologists are acknowledged to play a key role in this multidisciplinary setting. However, as a matter of fact, only minimal guidelines for specimen handling are on record. This means that in every day routine practice it is not uncommon for oncologists to deal with pathology reports where important parameters are missing (such as formal comments about therapy response). According to the lates...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Marchio, C., Maletta, F., Annaratone, L., Sapino, A. Tags: Article Source Type: research

Multiparametric and Multimodality Functional Radiological Imaging for Breast Cancer Diagnosis and Early Treatment Response Assessment
Breast cancer is the second leading cause of cancer death among US women, and the chance of a woman developing breast cancer sometime during her lifetime is one in eight. Early detection and diagnosis to allow appropriate locoregional and systemic treatment are key to improve the odds of surviving its diagnosis. Emerging data also suggest that different breast cancer subtypes (phenotypes) may respond differently to available adjuvant therapies. There is a growing understanding that not all patients benefit equally from systemic therapies, and therapeutic approaches are being increasingly personalized based on predictive bi...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Jacobs, M. A., Wolff, A. C., Macura, K. J., Stearns, V., Ouwerkerk, R., El Khouli, R., Bluemke, D. A., Wahl, R. Tags: Article Source Type: research

Neoadjuvant Chemotherapy: What Are the Benefits for the Patient and for the Investigator?
Neoadjuvant chemotherapy has several appealing potential benefits compared with classic adjuvant chemotherapy. Of these, the only proven benefit is to facilitate the surgical approach, either by converting an inoperable cancer to one that is operable, or by converting a patient who is felt to be a candidate for mastectomy to one who might be treated successfully with breast conserving therapy. Randomized trials comparing neoadjuvant chemotherapy with postoperative chemotherapy have failed to demonstrate prolongation of overall survival. The benefits of monitoring apparent response during neoadjuvant chemotherapy have not b...
Source: JNCI Monographs - June 10, 2015 Category: Cancer & Oncology Authors: Hayes, D. F., Schott, A. F. Tags: Article Source Type: research