Dynamic and subtype-specific interactions between tumour burden and prognosis in breast cancer.

We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR-/HER2-tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR-/HER2+ tumours among 131,178 patients with stage I-III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and < 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumours showed a persistent increase in mortality risk with an increase in tumour diameter, while the effect was modest in HER2+ tumours. Conversely, an increased number of metastatic nodes was accompanied by a persistently increased risk in HR-/HER2+ tumours, while the effect was minimal for HR-/HER2- tumours with > 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.

Associations between coronary artery stenosis detected by coronary computed tomography angiography and the characteristics of health checkup examinees in the Republic of Korea.

INTRODUCTION: This study was conducted on healthy adults without a diagnosis related to cardiovascular disease to investigate the associations between asymptomatic coronary artery stenosis and the characteristics of health checkup examinees. METHODS: This study was performed on 601 people (320 males and 281 females), who underwent coronary computed tomography angiography (CCTA), among health checkup examinees from January 2, 2015 to December 31, 2016. Those with any prior history of cardiovascular diseases, underwent coronary artery bypass grafting or coronary artery stenting in the past, those with atrial fibrillation, those suspected of contrast agent side effects, and those whose creatinine levels deviated from the normal range were excluded. RESULTS: The mean age was 58.7 ± 8.0 years. Coronary artery stenosis was detected in 173 people (28.8%), and the mean coronary artery stenosis rate was 25.8 ± 12.8%. Regression analysis showed that coronary artery stenosis was influenced significantly by age, gender, glycated hemoglobin (HbA1c), past smoking duration, current smoking duration, and number of glasses of alcohol consumed (p < 0.05). In terms of the relationship between the presence of coronary artery stenosis and lifestyle habits, amount of alcohol consumed per day (p = 0.03), and patients with a longer period of past (p < 0.001) and current smoking duration (p = 0.01) had a significant effect on coronary artery stenosis. CONCLUSION: These results suggest that men aged 60 years or older, who have consumed large amounts of alcohol and cigarettes for a long time, require continuous management through tests such as a health checkup, because of the high probability of coronary artery stenosis, even in those without specific symptoms.

Ultrafast x-ray absorption near edge spectroscopy of Fe3O4 using a laboratory based femtosecond x-ray source.

Ultrafast time-resolved x-ray absorption near edge spectroscopy (XANES) experiment was performed on a magnetite (Fe3O4) film using a femtosecond laser plasma x-ray source delivering Bremsstrahlung radiation. Ultrafast temporal evolution of the XANES of Fe3O4 following an excitation by an infra-red (IR) laser pulse was observed in a pump-probe scheme. The Fe K x-ray absorption edge shifts towards low energy upon IR excitation as much as 12 eV, which is mainly attributed to the charge transfer between the Fe ions. The shift in the absorption edge occurred within about 150 fs, typical time of non-thermal electronic redistribution. The charge transfer also causes an ultrafast increase in the IR transmission in the similar time scale.

Long-term effect of aromatase inhibitors on bone microarchitecture and macroarchitecture in non-osteoporotic postmenopausal women with breast cancer.

In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index. INTRODUCTION: AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer. METHODS: We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >-2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry. RESULTS: BMD significantly decreased from baseline to 5 years at the lumbar spine (-6.15%), femur neck (-7.12%), and total hip (-6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (-2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD. CONCLUSIONS: Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs.

Clinical benefit of nomogram for predicting positive resection margins in breast conserving surgery.

PURPOSE: Previously, we reported a nomogram for the prediction of positive resection margin (RM) after breast conserving surgery (BCS). This study was conducted to evaluate the clinical usefulness of the nomogram. METHODS: Prospective patients who underwent operations using the nomogram between July 2012 and August 2013 (nomogram group; N = 260) were compared with past control patients who underwent operations between July 2010 and October 2011 and underwent frozen section biopsy (FSB) without use of the nomogram (N = 266). In the nomogram group, an intraoperative assessment of RM using FSB was only performed when the nomogram score was higher than predefined cut-off (>80). In addition, we conducted retrospective analysis of additional 181 patients who received BCS in another institute (Kyoto University Hospital). These patients did not undergo FSBs for RMs. RESULTS: Of 260 patients, 161 (61.9%) presented low nomogram scores and avoided FSB. The surgical decision to use the nomogram did not significantly increase reoperation rate due to positive RM compared with the control FSB group (4.6% vs. 3.8%, p = 0.47). The surgery time was significantly reduced by 18.1% (mean 14.7 min) in nomogram group (p < 0.001). Of 99 nomogram high-score patients, 14 presented with positive RM on FSB and 11 of them avoided reoperation. In the Kyoto cohort, the reoperation rate was significantly lower in low-score patients than in high-score patients (2.7% vs. 11.4%, p < 0.001). CONCLUSIONS: We showed that our nomogram is useful to reduce FSBs without increasing reoperation rate for surgeons who perform routine FSBs. For most surgeons, it can give useful information about the possibility of tumor-positive RMs.

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

BACKGROUND: We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. PATIENTS AND METHODS: From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. RESULTS: The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. CONCLUSIONS: We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process.

Mediating effect of stress on the association between early trauma and psychological distress in Korean college students: a cross-sectional observational study.

ACCESSIBLE SUMMARY: What is known on the subject? Despite the increase of studies into the predictors of psychological distress, few have attempted to address the mediation of stress in the relationship between early trauma and psychological distress. What does this paper add to existing knowledge? In this study, college students with trauma exposure before the age of 18 years reported high levels of college life stress and psychological distress. In addition, of the subcategories of early trauma, emotional abuse was most highly correlated with current stress and psychological distress. This paper confirmed the partial mediating effect of stress between early trauma and psychological distress among Korean college students. In other words, this study found a direct effect of early trauma on current psychological distress and an indirect effect of early trauma on psychological distress mediated through life stress. What are the implications for practice? Early trauma and stress should be considered when developing interventions for college students' mental health, although individuals with trauma exposure have difficulties disclosing their traumatic event. Therefore, we suggest that stress management may be easier to apply and more effective in promoting college students' mental health than trauma-focused interventions. INTRODUCTION: Research has shown that early trauma and stress may affect current psychological distress. However, few studies have attempted to address the mediation of stress between early trauma and psychological distress. AIM: This cross-sectional observational study aimed to examine the mediating effects of stress on the association between early trauma and psychological distress in Korean college students. METHOD: Participants included 216 college students (51.4% male) who completed self-report questionnaires assessing early trauma, college life stress, and psychological distress. RESULTS: Early trauma, stress, and psychological distress were significantly correlated. Of the subcategories of early trauma, emotional abuse was most highly correlated with stress and psychological distress. The bootstrapping results indicate that stress is a partial mediator between early trauma and psychological distress after controlling for covariates including socioeconomic status, habitation status, and gender. DISCUSSION: The results imply that both early trauma and stress should be considered when developing interventions for college students' mental health. However, individuals with trauma exposure tend to have difficulties disclosing their traumatic event. Therefore, we suggest that stress management may be more feasible and effective in promoting college students' mental health than trauma-focused interventions.

Association between information provision and decisional conflict in cancer patients.

BACKGROUND: In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). PATIENTS AND METHODS: We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. RESULTS: More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30-0.97] and support (aOR, 0.53; 95% CI 0.33-0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26-0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27-0.77). CONCLUSION: This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.

Effect of cosmetic outcome on quality of life after breast cancer surgery.

PURPOSE: Studies regarding the effects of aesthetic outcomes after breast cancer surgery on quality of life (QoL) have yielded inconsistent results. This study analyzed the aesthetic outcomes and QoL of women who underwent breast conserving surgery (BCS) or total mastectomy with immediate reconstruction (TMIR) using objective and validated methods. PATIENTS AND METHODS: QoL questionnaires (EORTC QLQ-C30, BR23, and HADs) were administered at least 1 year after surgery and adjuvant therapy to 485 patients who underwent BCS, 46 who underwent TMIR, and 87 who underwent total mastectomy (TM) without reconstruction. Aesthetic results were evaluated using BCCT.core software and by a panel of physicians. Patients' body image perception was assessed using the body image scale (BIS). RESULTS: QoL outcomes, including for social and role functioning, fatigue, pain, body image, and arm symptoms, were significantly better in the BCS and TMIR groups than in the TM group (p<0.05 each). BIS was significantly better in the BCS than in the TM or TMIR group (p<0.001 each). In the BCS and TMIR groups, general QoL factors were not significantly associated with objective cosmetic outcomes, except for body image in the QLQ-BR23. In contrast, patients with poorer BIS score reported lower QoL in almost all items of the QLQ-C30, BR23, and HADS (p<0.05 each). CONCLUSION: In conclusion, BCS and TMIR enhanced QoL compared with TM. Among BCS and TMIR patients, objectively measured cosmetic results did not affect general QoL. Self-perception of body image seems to be more important for QoL after breast cancer surgery.

Cytokeratin19 induced by HER2/ERK binds and stabilizes HER2 on cell membranes.

Cytokeratin19 (KRT19) is widely used as a biomarker for the detection of disseminated tumors. Using an LC-MS/MS proteomics approach, we found that KRT19 was upregulated in HER2-overexpressing cells and tissues. KRT19 expression was induced by HER2-downstream ERK at the transcriptional level. Another HER2-downstream kinase, Akt, was found to phosphorylate KRT19 on Ser35 and induce membrane translocation of KRT19 and remodeling of KRT19 from filamentous to granulous form. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. Silencing of KRT19 by shRNA resulted in increased ubiquitination and destabilization of HER2. Moreover, treatment of KRT19 antibody resulted in downregulation of HER2 and reduced cell viability. These data provide a new rationale for targeting HER2-positive breast cancers.

Effect of endoscopy screening on stage at gastric cancer diagnosis: results of the National Cancer Screening Programme in Korea.

BACKGROUND: Although gastric cancer screening is common among countries with a high prevalence of gastric cancer, there is little data to support the effectiveness of this screening. This study was designed to determine the differences in stage at diagnosis of gastric cancer according to the screening history and screening method (upper gastrointestinal series (UGIS) vs endoscopy). METHODS: The study population was derived from the National Cancer Screening Programme (NCSP), a nationwide organised screening programme in Korea. The study cohort consisted of 19 168 gastric cancer patients who had been diagnosed in 2007 and who were invited to undergo gastric cancer screening via the NCSP between 2002 and 2007. RESULTS: Compared with never-screened patients, the odds ratios for being diagnosed with localised gastric cancer in endoscopy-screened patients and UGIS-screened patients were 2.10 (95% CI=1.90-2.33) and 1.24 (95% CI=1.13-1.36), respectively. CONCLUSIONS: Screening by endoscopy was more strongly associated with a diagnosis of localised stage gastric cancer compared with screening by UGIS.

Ahnak functions as a tumor suppressor via modulation of TGFß/Smad signaling pathway.

We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor ß (TGFß) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFß-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFß signaling.

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Effect of multiple invasive foci on breast cancer outcomes according to the molecular subtypes: a report from the Korean Breast Cancer Society.

BACKGROUND: In this study, the prognostic impact of the presence of the multifocal or multicentric tumor (MMT) and its association with molecular subtypes were investigated. PATIENTS AND METHODS: We investigated the breast cancer metastasis and survival in patients with multifocal or multicentric invasive foci in the same breast. The study population includes 2882 patients in the Seoul National University Hospital Breast Care Center (SNUHBCC) dataset and 41 179 patients in Korean Breast Cancer Registry (KBCR) dataset. RESULTS: From SNUHBCC dataset, we observed a significant role of MMT in developing distant metastasis and death when the tumors were triple-negative subtype. This subtype-specific prognostic importance of MMT in overall survival was also seen in KBCR dataset (HR, 1.32; 95% CI, 1.02-1.69). In tumors <2 cm, the hazard ratios (HRs) for node metastasis and death were similar along the tumor size change in triple-negative subtype, while other subtypes showed a stepwise increment, suggesting the biologic importance of small invasive foci in this subtype. CONCLUSIONS: Our results demonstrate the prognostic importance of MMT in patients with triple-negative breast cancers. Small additional invasive foci in triple-negative breast cancer patients should be considered as clinically relevant tumor deposits.

SVCT-2 in breast cancer acts as an indicator for L-ascorbate treatment.

L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.

Daily skin care habits and the risk of skin eruptions and symptoms in cancer patients.

BACKGROUND: Cancer patients are at high risk for skin problems because rapidly proliferating skin cells are susceptible to anticancer therapies. However, the effects of daily skin care habits on development of skin problems in cancer patients have rarely been studied. PATIENTS AND METHODS: We conducted a survey of daily skin care habits and the presence of skin problems in 866 cancer patients. RESULTS: Hot water bath>1 h significantly increased the risk of definite eruptions [odds ratio (OR) 4.09] and the risk of itching or pain on the skin (OR 1.73). Diligent use of moisturizers did not decrease the risk of definite eruptions and symptoms, and daily bathing, scrubbing off the skin while bathing, and sun protection did not influence the risk of definite eruptions and symptoms. Subgroup analysis of 183 breast cancer patients showed results similar to the total results, including that hot water bath>1 h significantly increased the risk of definite eruptions (OR 3.41). CONCLUSIONS: Being a cross-sectional study, our study could not prove causality. However, at the present stage of knowledge, avoidance of hot water baths of protracted duration should be first emphasized in patient education to prevent skin problems in cancer patients.

The influence of hospital volume and surgical treatment delay on long-term survival after cancer surgery.

BACKGROUND: We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer patients. METHODS: Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers. RESULTS: Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival [adjusted hazard ratio (aHR) = 1.36-1.86] than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal [aHR = 1.28; 95% confidence interval (CI), 1.17-1.40] and breast (aHR = 1.59; 95% CI, 1.37-1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78-3.81). CONCLUSION: Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.

Hard X-ray microbeam lithography using a Fresnel zone plate with a long focal length.

Focused hard X-ray microbeams for use in X-ray nanolithography have been investigated. A 7.5 keV X-ray beam generated at an undulator was focused to about 3 µm using a Fresnel zone plate fabricated on silicon. The focused X-ray beam retains a high degree of collimation owing to the long focal length of the zone plate, which greatly facilitates hard X-ray nanoscale lithography. The focused X-ray microbeam was successfully utilized to fabricate patterns with features as small as 100 nm on a photoresist.

Coherent diffraction surface imaging in reflection geometry.

We present a reflection based coherent diffraction imaging method which can be used to reconstruct a non periodic surface image from a diffraction amplitude measured in reflection geometry. Using a He-Ne laser, we demonstrated that a surface image can be reconstructed solely from the reflected intensity from a surface without relying on any prior knowledge of the sample object or the object support. The reconstructed phase image of the exit wave is particularly interesting since it can be used to obtain quantitative information of the surface depth profile or the phase change during the reflection process. We believe that this work will broaden the application areas of coherent diffraction imaging techniques using light sources with limited penetration depth.

Focal amplification and oncogene dependency of GAB2 in breast cancer.

DNA amplifications in breast cancer are frequent on chromosome 11q, in which multiple driver oncogenes likely reside in addition to cyclin D1 (CCND1). One such candidate, the scaffolding adapter protein, GRB2-associated binding protein 2 (GAB2), functions in ErbB signaling and was recently shown to enhance mammary epithelial cell proliferation, and metastasis of ERBB2 (HER2/neu)-driven murine breast cancer. However, the amplification status and function of GAB2 in the context of amplification remain undefined. In this study, by genomic profiling of 172 breast tumors, and fluorescence in situ hybridization validation in an independent set of 210 scorable cases, we observed focal amplification spanning GAB2 (11q14.1) independent of CCND1 (11q13.2) amplification, consistent with a driver role. Further, small interfering RNA (siRNA)-mediated knockdown of GAB2 in breast cancer lines (SUM52, SUM44PE and MDA468) with GAB2 amplification revealed a dependency on GAB2 for cell proliferation, cell-cycle progression, survival and invasion, likely mediated through altered phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling. GAB2 knockdown also reduced proliferation and survival in a cell line (BT474) with ERBB2 amplification, consistent with the possibility that GAB2 can function downstream of ERBB2. Our studies implicate focal amplification of GAB2 in breast carcinogenesis, and underscore an oncogenic role of scaffolding adapter proteins, and a potential new point of therapeutic intervention.