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Desmedt and colleagues published two articles, one in the June 1, 2007 issue, and the other in the August 15, 2008, issue of Clinical Cancer Research, that showed gene-expression signatures to be proliferation driven and time dependent, with their prognostic power decreasing with increasing follow-up years. Moreover, the articles showed that immune response is a crucial determinant of prognosis in the HER2-positive and estrogen receptor–negative/HER2-negative subtypes, providing a rationale to further explore the role of the antitumor immune response in these breast cancer subtypes. Clin Cancer Res; 21(21); 4743–6. ©2015 AACR.See related articles by Desmedt et al., Clin Cancer Res 2007;13(11) June 1, 2007;3207–14 and Desmedt et al., Clin Cancer Res 2008;14(16) August 15, 2008;5158–65.

Summary of the commercially available proliferation-based gene-signatures in breast cancer

Desmedt and colleagues published two articles, one in the June 1, 2007 issue, and the other in the August 15, 2008, issue of Clinical Cancer Research, that showed gene-expression signatures to be proliferation driven and time dependent, with their prognostic power decreasing with increasing follow-up years. Moreover, the articles showed that immune response is a crucial determinant of prognosis in the HER2-positive and estrogen receptor–negative/HER2-negative subtypes, providing a rationale to further explore the role of the antitumor immune response in these breast cancer subtypes. Clin Cancer Res; 21(21); 4743–6. ©2015 AACR. See related articles by Desmedt et al., Clin Cancer Res 2007;13(11) June 1, 2007;3207–14 and Desmedt et al., Clin Cancer Res 2008;14(16) August 15, 2008;5158–65.

No biomarker beyond HER2 itself, which suffers from a low positive predictive value, has demonstrated clinical utility in breast cancer, despite numerous attempts to improve treatment tailoring for the growing number of anti-HER2 targeted therapies. This prompted us to examine the body of evidence, using a systematic approach, to identify putative predictive biomarkers in HER2-positive breast cancer, and discuss the hitherto failure to address the needs of patients. In the future, it is hoped immune-based biomarkers will predict benefit from anti-HER2 treatments in the neoadjuvant and adjuvant settings. In advanced-stage disease, the quantification of tumour heterogeneity using molecular-imaging technology has generated informative data on the success or failure of the antibody-drug conjugate T-DM1. Treatment tailoring remains a high priority, in cost-constrained health-care systems, but such tailoring will require a dramatic shift in the way translational research is being conducted, with the establishment of large, easily accessible, and well-annotated databases of candidate predictive biomarkers. Single-centre biomarker research should become a thing of the past.

Background: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)–positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. Results: One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Conclusions: Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randomized clinical trials.

Natural resources that are “commons” or held in public trust are notoriously difficult to govern. 1 In the absence of exclusive property rights, authorities face the twin challenges of setting limi...

Circulating nucleic acids such as DNA and microRNA are released and circulate in the blood of cancer patients. In breast cancer, free circulating nucleic acids are being explored as potential blood biomarkers for real-time tumor monitoring. In the past decades, increasing evidence has emerged indicating potential use of circulating DNA for assessment of tumor burden and for tumor genomic and epigenetic profiling. MicroRNA profiling studies also suggest potential utility for breast cancer screening, prognosis evaluation and interrogating mechanisms of therapy resistance and tumor biology. However, a variety of preanalytical considerations must be contemplated and ultimately clinical validity and utility must be demonstrated. This book chapter will explore the main methods to detect and analyze circulating tumor DNA and circulating microRNA, and the clinical applications for circulating free nucleic acids analysis in breast cancer.

The current studies examined relations between mothers' trust in organismic development, autonomy sup- portive parenting, and adaptation among mothers and their young children. Study 1 showed that trust in organismic development was distinct from optimism, neuroticism, and social desirability whereas it correlated with having relaxed expectations for developmental milestones and making fewer social comparisons about one's child. Study 2 used observational methods to demonstrate a significant link between trust in organismic development and mothers behaving in an autonomy-supportive rather than control- ling manner toward their 1-year-old child during puzzle solving activities. Study 3 used a 1 year prospective design to show that trust in first time mothers was associated with better maternal and child adaptation over time, controlling for initial levels of adaptation and child temperament. Study 4 explored possible social/political antecedents of trust in organismic development by comparing the beliefs of first time mothers from Canada and Norway. The four studies suggest that trust in organismic development fosters autonomy supportive parenting practices and positive maternal and child adaptation. These findings are discussed from the perspective of self-determination theory.

There is increasing availability of technologies that can interrogate the genomic landscape of an individual tumor; however, their impact on daily practice remains uncertain. We conducted a 28-item survey to investigate the current attitudes towards the integration of tumor genome sequencing in breast cancer management. A link to the survey was communicated via newsletters of several oncological societies, and dedicated mailing by academic research groups. Multivariable logistic regression modeling was carried out to determine the relationship between predictors and outcomes. 215 physicians participated to the survey. The majority were medical oncologists (88%), practicing in Europe (70%) and working in academic institutions (66%). Tumor genome sequencing was requested by 82 participants (38%), of whom 21% reported low confidence in their genomic knowledge, and 56% considered tumor genome sequencing to be poorly accessible. In multivariable analysis, having time allocated to research (OR 3.37, 95% CI 1.84-6.15, p < 0.0001), working in Asia (OR 5.76, 95% CI 1.57 - 21.15, p = 0.01) and having institutional guidelines for molecular sequencing (OR 2.09, 95% 0.99-4.42, p = 0.05) were associated with a higher probability of use. In conclusion, our survey indicates that tumor genome sequencing is sometimes used, albeit not widely, in guiding management of breast cancer patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Every cancer triggers an immune response that constitutes an important first-line protection against cancer progression. In breast cancer, there is an increasing awareness of the relationship between the immune system and tumor evolution. The tumor microenvironment is composed of a variety of immune cells that can control or arrest malignant progression. Chemotherapy and targeted therapy have been shown to modulate this immune microenvironment. Recently, tumor-infiltrating lymphocytes have emerged as a predictive and prognostic biomarker in early breast cancer. In addition, immune gene expression signatures have been shown to be associated with prognosis in triple-negative and human epidermal growth factor receptor 2-positive breast cancer. Such findings have increased interest in the development of immunotherapeutic agents for breast cancer, and multiple clinical trials of anticancer vaccines and immune checkpoint inhibitors are ongoing. In this review, we summarize what is known about the relationship between immunity and breast carcinoma, explore the relevance of this information to the clinical and research settings, and give a portrait of new therapeutic strategies using immunotherapy in breast cancer.

Purpose of review: The aim of this review is to highlight the recent advances (in the past 12 months) concerning circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in oncology. Recent findings: The value of CTCs as a prognostic biomarker is now well validated in breast, colon, and prostate cancer, but no trial has yet demonstrated that modifying treatment according to CTCs is superior to standard of care. Ongoing trials are addressing the clinical utility of CTCs. Moreover, there is emerging evidence about the potential of CTCs as a tumor tissue source to analyze protein and RNA expression, DNA mutations and drug sensitivity. ctDNA is a specific biomarker associated with tumor burden, and small studies have shown an association with worse outcome; prospective clinical studies on the prognostic and predictive value of ctDNA are needed. ctDNA can be used for tumor molecular profiling, with the potential advantage to encompass the spectrum of mutations present in the tumor. Summary: CTCs and ctDNA are promising new biomarkers in oncology, with potential clinical applications for monitoring and for comprehensive molecular profiling of cancer. For each assay, demonstration of analytical and clinical validity, as well as clinical utility in prospective clinical trials is needed before implementation in clinical practice.

In 2015, academic-led trials provided evidence for safe de-escalation of adjuvant treatment in early stage breast cancer and answered important questions related to adjuvant regional irradiation and optimal first-line chemotherapy in advanced-stage disease. Furthermore, the development of novel therapies and potential tools for treatment tailoring will offer new hope to patients with breast cancer.

The present investigation examined motivation for parenting and some of its correlates in parents and children. The data came from samples of 151 first-time mothers of infants, 153 mothers of middle school children, and 260 mothers and fathers of high school children. Parents provided self-report data about their motivation in their parenting role as well as reports of role satisfaction, parental competence, child temperament, and parenting styles. Using three samples, factor analyses confirmed the distinction between autonomous and controlled forms of parenting motivation. Autonomous motivation refers to investing in the parenting role because it is interesting and meaningful whereas controlled motivation refers to investment based on external or internal pressures. Results showed that autonomous motivation was associated concurrently with parenting satisfaction and competence as well as with authoritative and autonomy-supportive parenting styles. Child temperament was unrelated to parenting motivation, but mothers reported greater autonomous motivation for girls than boys and for younger children rather than older children. Autonomous parenting motivation was associated with children reporting autonomy supportive parenting and high levels of well-being. A prospective analysis showed that controlled parenting motivation in first time mothers was associated with reductions in parenting satisfaction as infants became toddlers. A similar analysis showed that autonomous parenting motivation was associated with children developing fewer behavior problems whereas controlled motivation was associated with children developing more behavioral problems. The present findings highlight the heuristic value of assessing why parents invest themselves in the parenting role.

The present study examined whether reactive and reflective autonomy moderated individuals' responses to expert influence. Participants were given the opportunity to win money at a racetrack betting task for which they were provided with objective information about horses' previous perfor- mances along with specific expert recommendations. The experts were made to look either credible or noncredible by manipulating information on the success rate of their previous predictions. The results showed that the two forms of

604Background: The optimal treatment of regional nodal areas following breast-conserving surgery (BCS) is a source of debate. Two randomized trials recently demonstrated that regional nodal irradiation (RNI) can reduce the risk of recurrence in early breast cancer; however,these trials were conducted in the pre-trastuzumab era.Whether these results are applicable to HER2-positive breast cancer patients treated with anti-HER2 targeted therapy, is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer, who were enrolled in the ALTTO phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). Secondary objectives included regional recurrences and overall survival (OS). A multivariate cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timin...

Background: Personalized medicine is a rising paradigm in cancer care. The identification of pathways involved in carcinogenesis along with the development of targeted therapies has revolutionized cancer treatment. There is increasing availability of technologies that can interrogate the genomic landscape of the tumor; however, it is still uncertain whether such platforms are used in clinical practice. Methods: We conducted a 28-item survey to investigate the current use of tumor molecular sequencing in the management of breast cancer patients. A link to the online survey was communicated via various platforms such as the European Society for Medical Oncology (ESMO) and European School of Oncology (ESO) newsletter, and via a dedicated mailing by the Breast International Group (BIG) and other academic groups. Descriptive statistical analysis and Fisher's exact tests were applied to explore potential association between the demographic characteristics and responses. Results: A total of 211 physicians from 35 countries participated to the study between the 9 March and 3 June 2015, with 92% fully completed questionnaires. The mean age of the participants was 45 years (range 27-77). The majority of responders were medical oncologists (88%), practicing in Europe (69%) and working in academic institutions (66%). 62% (130/211) of participants had never requested tumor molecular sequencing for breast cancer patients. Working in academic institutions and having more time allocated to research were associated with the use of tumor molecular sequencing (p = 0.007 and 0.009, respectively). For the 81 participants that used tumor molecular sequencing in the past (Table 1), there was a significant association between accessibility and frequency of use (p=0.02). 92% (181/211) of participants claimed that they would probably use tumor molecular sequencing more often if it was more accessible. Lack of funding and lack of access to the technology were the main reasons for poor endorsement. 89% of participants believe that tumor molecular sequencing will play a major role in the management of breast cancer patients in the future. Current weak evidence and poor access to matched targeted therapy are the main concerns against a wider use of these platforms in clinical practice. Table 1. Summary of replies from the 81 participants that used tumor molecular sequencing for breast cancer patientsQuestionResponseN (%)In what percentage of your breast cancer patients has tumor molecular sequencing been performed at least once?≤5%55 (68%) >5%26 (32%)How often do the results lead to enrollment in a clinical trial?≤10%53 (65%) >10%28 (35%)How confident are you in interpreting tumor sequencing results?Not at all/A little17 (21%) Somewhat/Highly64 (79%)Do you consider molecular sequencing platforms accessible?Not at all/A little45 (55%) Somewhat/Highly36 (45%) Conclusion: Our survey indicates that molecular sequencing platforms are sometimes used, albeit not widely in guiding management of breast cancer patients. Poor accessibility may contribute to the low frequency of use, but lack of evidence and poor access to matched targeted therapy are also major concerns. Citation Format: Gingras I, Sonnenblick A, Dolci S, de Azambuja E, Paesmans M, Delaloge S, Piccart MJ, Sotiriou C, Michail I, Azim Jr HA. The role of precision medicine in "real-life" management of breast cancer patients: A survey assessing the current use and attitudes towards tumor molecular sequencing in clinical practice. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-04-13.

This study tested the degree to which a need-supportive family environment influences adolescents' endorsement of the value priorities that their mothers wish for them. Mothers and their adolescents (N=280) rated the importance of three intrinsic values (personal growth, close relationships, and community contribution) and three extrinsic values (wealth, fame, and attractiveness). Results revealed that mothers placed greater emphasis on intrinsic over extrinsic values than did adolescents. Furthermore, the congruence of mothers' and adolescents' emphasis on intrinsic values was moderated by the extent to which adolescents experienced satisfaction of their basic needs for autonomy, relatedness, and competence at home. Finally, the well-being of both adolescents and mothers was associated with the degree to which they prioritized intrinsic over extrinsic values. Implications for research on the transmission of values and goals are discussed.

Self-determination theory proposes that prioritizing intrinsic life goals, such as community involvement, is related to well-being, whereas focusing on extrinsic life goals, such as financial success, is associated with lower well-being and that parenting influences the type of life goals that youth adopt. In a sample of 515 Chinese (56% female, mean age = 15.50) and 567 North American (52% male, mean age = 14.17) adolescents, a model of the relationships between parenting, life goals, and well-being was investigated and confirmed for intrinsic life goals. Across societies, autonomy-supportive parenting was associated with the endorsement of intrinsic life goals, which in turn was associated with well-being. Intrinsic life goals partially mediated the relationship between parental autonomy-support and well-being. These findings suggest that, cross-culturally, prioritizing intrinsic life goals is related to increased well-being among adolescents and that parents could encourage intrinsic life goals by being supportive of their children’s autonomy.

Self-determination theory posits that satisfaction of three basic psychological needs—autonomy, competence, and relatedness—are required for psychological well-being, and a recent study showed that the balance in the satisfaction of these three needs independently affects well-being. The present investigation builds on these findings by examining the balance of adolescents' need satisfaction across distinct life contexts. The results of three studies show that adolescents who experience a balance of need satisfaction across important life contexts, including at school, at home, with friends, and in part-time jobs, reported higher well-being and better school adjustment. This finding emerged consistently across four countries and across multiple measures of school adjustment, including teacher reports. Together, these results support previous research that highlights the importance of consistency for psychological functioning.

Recently, 3 different meta-analytic reviews of the literature concerning the effects of extrinsic rewards on intrinsic motivation have appeared, including that by Deci, Koestner, and Ryan (1999) in this issue. Interestingly, despite their common focus, these reviews have offered dramatically opposed bottom-line conclusions about the meaning and implications of this literature. In this comment, the authors examine differences among these 3 reviews and conclude that the findings of this literature have been more accurately captured by the reviews of Deci et al. and Tang and Hall (1995) than by that of Cameron and Pierce (1994). More broadly, the authors also suggest that there may be significant short- and long-term costs to the unthinking or automatic use of meta-analysis with theoretically derived, procedurally diverse, and empirically complex literatures like that concerning extrinsic rewards and intrinsic motivation.