Abstract: Clinical and preclinical data support a significant role for inhibitors of the cyclin-dependent kinases (CDKs) 4 and 6 in the treatment of patients with breast cancer. Recently, based on data showing improvement in progression-free survival, the use of palbociclib (Ibrance; Pfizer, Inc.) in combination with endocrine agents was approved to treat patients with hormone receptor-positive advanced disease. Importantly, 2 other CDK4/6 inhibitors, abemaciclib (LY2835219; Lilly) and ribociclib (LEE011; Novartis), are in the late stage of clinical development. In this review, we will focus on clinical data on these 2 new drugs, highlighting their differences compared to palbociclib in terms of single-agent activity, central nervous system penetration, and common adverse events. In addition, we will present the ongoing clinical trials and discuss future directions in the field.

Abstract: Background: This study was performed to compare the mammographic, sonographic, and magnetic resonance imaging (MRI) characteristics of phyllodes tumors and fibroadenomas, which may resemble each other. Methods: Preoperative mammograms, B-mode and Doppler sonograms, and dynamic breast MRIs of 72 patients with pathologically proven fibroadenomas and 70 patients with pathologically proven phyllodes tumor were evaluated in this retrospective study. Statistical significance was evaluated using chi-square and Fisher's exact tests. Correlations in lesion size among radiological methods were examined by Pearson's correlation analysis. Results: The features that differed on mammogram were size, shape, and margin of the mass. Sonograms showed significant differences in size, shape, margin, echo pattern, and vascularization of the mass. Pearson's correlation analysis showed strong agreement among radiological methods in terms of assessment of size. Tumor size ≥ 3 cm, irregular shape, microlobulated margins, complex internal echo pattern, and hypervascularity were significant findings of phyllodes tumors. Internal cystic areas on MRI were frequently associated with phyllodes tumors. Conclusion: Mammographic, sonographic, and MRI findings of fibroadenomas and phyllodes tumors could help radiologists to ascertain imaging-histological concordance and guide clinicians in their decision making regarding adequate follow-up or the necessity of biopsy.

Abstract: Background: This study was aimed at comparing the quality of life, body image, and perceived social support in women with breast cancer surgery. Patients and Methods: Patients receiving breast-conserving surgery (BCS) (n = 72), mastectomy alone (n = 44), and mastectomy with breast reconstruction (n = 41) were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the EORTC Breast Cancer Module (QLQ-BR23), the Body Image Scale (BIS) and the Multidimensional Scale of Perceived Social Support (MSPSS). Results: The results indicated that the BCS group had a better body image compared with the other 2 groups and better role functioning compared with the mastectomy-alone group. In the reconstruction group, body image correlated with perceived social support, especially from family and significant others. Conclusion: These results suggest that a positive perception of a supportive social network can help women with breast reconstruction to better cope with the psychological effects of surgery on their body image.

Abstract: Background: The etiology of lymphedema is multifactorial, and definition criteria of lymphedema, its limitation, and follow-up must be considered in studies related to risk factors. The aim of this study is to evaluate risk factors related to arm lymphedema in a cohort study with a long follow-up. Patients and Methods: The study was performed in 622 breast cancer patients. The main endpoint reported was the presence of clinical lymphedema reported in medical records. Univariate and multivariate regression analyses were performed to identify factors related to lymphedema. Results: 66.4% of the patients were submitted to mastectomy, 88.4% to level III axillary lymphadenectomy, 34.9% to radiotherapy in the supraclavicular fossa, and 4.3% to axillary radiotherapy. The mean follow-up was 96.7 months. 45 patients (7.2%) developed lymphedema, of which 82.2% had developed lymphedema at 60 months. Univariate regression analysis showed that supraclavicular radiotherapy, adjuvant/palliative chemotherapy, ≥ 15 lymph nodes dissected, and axillary surgery increase the lymphedema rate by 1.87, 2.28, 2.03, and 6.17, respectively. Adjusted multivariate regression analysis showed that the combination of axillary dissection and number of lymph nodes dissected was the main factor related to lymphedema (p = 0.017). Conclusion: In the pre-sentinel era, axillary dissection and the number of lymph nodes resected are related to 10-year lymphedema.

Abstract: Background: Breast-conserving surgery (BCS) in patients with large tumors shrunk by neoadjuvant chemotherapy (NCT) remains controversial. We conducted a meta-anal

Abstract: Immune checkpoints are crucial for the maintenance of self-tolerance and for the modulation of immune responses in order to minimize tissue damage. Tumor cells take advantage of these mechanisms to evade immune recognition. A significant proportion of tumors, including breast cancers, can express co-inhibitory molecules that are important formediating the escape from T cell-mediated immune surveillance. The interaction of inhibitory receptors with their ligands can be blocked by specific molecules. Monoclonal antibodies (mAbs) directed against the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and, more recently, against the programmed cell death protein 1 (PD1), have been approved for the therapy of melanoma (anti-CTLA4 and anti-PD1 mAbs) and non-small cell lung cancer (anti-PD1 mAbs). Moreover, inhibition of PD1 signaling has shown extremely promising signs of activity in breast cancer. An increasing number of molecules directed against other immune checkpoints are currently under clinical development. In this review, we summarize the evidence supporting the implementation of checkpoint inhibition in breast cancer by reviewing in detail data on PD-L1 expression and its regulation. In addition, opportunities to boost anti-tumor immunity in breast cancer with checkpoint inhibitor-based immunotherapies alone and in combination with other treatment options will be discussed.

Abstract: There is clear evidence that the immune system plays an essential role in tumor defense. By determining tumor-infiltrating lymphocytes (TILs), the individual immunological response becomes more apparent and measurable. In breast cancer, high levels of TILs are associated with a more favorable clinical course. In this review, we describe how TILs are determined with emphasis on daily routine diagnostics. We further discuss their impact as a prognostic and predictive biomarker in the neoadjuvant and adjuvant therapy setting as well as in residual disease. We also discuss their potential future implications on further stratifying prognostic subgroups of breast cancer, thereby possibly influencing future therapy considerations.

Abstract: E75 is an immunogenic peptide derived from the human epidermal growth factor receptor 2 (HER2) protein. A large amount of preclinical work evaluated the immunogenicity of E75, after which phase I trials investigated using E75 mixed with an immunoadjuvant as a vaccine. Those studies showed the vaccine to be safe and capable of stimulating an antigen-specific immune response. Subsequent to that, our group conducted trials evaluating E75 + granulocyte macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting. The studies enrolled node-positive and high-risk node-negative breast cancer patients, with the goal being to determine if vaccination could decrease the recurrence risk. The studies included 187 evaluable patients: 108 vaccinated ones and 79 controls. The 5-year disease-free survival for the vaccinated patients was 89.7% compared to 80.2% for the control patients, a 48% reduction in relative risk of recurrence. Based on these data, E75 + GM-CSF, now known as NeuVax™, is being evaluated in a phase III trial. In this article, we review preclinical data and results of the early-phase trials and provide an update on the ongoing phase III study. We also present additional strategies for employing the vaccine to be included as a component of combination immunotherapy as well as in the setting of ductal carcinoma in situ as an initial step towards primary prevention.

Abstract: Background: This article describes the demographic, clinical, pathological and prognostic features of breast nodular fasciitis through a comprehensive review of t

Abstract: Background: The aim of this study was to determine whether the indicators obtained from intravoxel incoherent motion (IVIM) imaging can improve the characterizati

Abstract: Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance. Understanding the way in which resistance develops is therefore essential for developing treatment approaches that can prevent or reverse endocrine resistance. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role here. As a result of the numerous interactions involved, complex issues arise that need to be taken into account in the development and use of therapeutic agents. In addition, this signaling pathway is the one that most frequently undergoes mutations in breast cancer. The prognostic and predictive significance of individual mutations has not yet been fully explained, but it might provide a basis for patient selection in clinical studies. Initial research results on the use of PI3K inhibitors suggest that this may be a highly promising therapeutic approach, with an acceptable side effect profile.

Abstract: Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of mammary stroma mostly described as an incidental microscopic finding. Clinically, it can manifest as a palpable, well-circumscribed breast mass or in rare cases as a diffuse bilateral process causing massive breast enlargement. The most postulated theory for aetiology of this condition is hormonal stimulation of mammary myofibroblasts, particularly by progesterone. A definite diagnosis of PASH is based on typical pathological findings like stromal hyperplasia and empty slit-like channels positive for myofibroblastic and negative for endothelial markers. The main clinical differential diagnosis is a fibroadedoma or phylloid tumour, and histologically a low-grade angiosarcoma. There are less than 200 cases of tumorous PASH and less than 20 of diffuse PASH reported so far. Here we present a case report of huge diffuse PASH, that is, to our knowledge, the first in a pregnant woman.

Abstract: led to a focus of neoadjuvant chemotherapy in triple negative and HER2-positive patients, with some studies only enrolling those 2 patient groups [8, 9]. Knowing that patients with some tumor types more often achieve pCR than others and that the connection between pCR and prognosis differs between subgroups, one recent focus of research is to differentiate patients who benefit from pCR from those in which a complete disappearance of the tumor does not have a larger prognostic effect. One example is the subgroup of triple negative patients with a BRCA mutation: in a clinical cohort treated neoadjuvantly with anthracyclines and taxanes a prognostic effect of pCR could only be shown in patients with a wildtype BRCA status [10]. Similarly, patients with a PIR3K mutation in their tumor often achieve a pCR after neoadjuvant chemotherapy combined with anti-HER2 therapy. However, a PI3K mutation does not seem to have influence on prognosis [11]. This shows that we still have a lot to learn concerning the connection between pCR and prognosis. It was tried to establish pCR as a surrogate marker for prognosis, which could lead to the approval of neoadjuvant therapies. However, the combined analysis of almost 12,000 patients from 12 international trials did not validate pCR as a surrogate marker for prognosis [3]. In a subgroup analysis, the correlation between pCR and prognosis was largest in HER2-positive patients [3, 12], indicating that further research on how to use response to neoadjuvant therapy for drug development might be most successful in this breast cancer subtype. In this issue of Breast Care, Kolberg and colleagues [13] present the 4-year follow-up of patients who achieved pCR after neoadjuvant treatment with a combination of docetaxel, carboplatin, and weekly TCH. Patients who have residual disease after neoadjuvant chemotherapy are a clinical problem, as they represent a subgroup with very unfavorable prognosis. Novel therapy concepts consider these patients for an additional adjuvant therapy in so-called postNeoadjuvant chemotherapy was first introduced for the treatment of larger tumors in order to reduce tumor size and possibly increase the likelihood for a breast conserving therapy; however, after decades of clinical use of neoadjuvant chemotherapy, it can be considered as a standard chemotherapy option for any patient who has an indication for neoadjuvant chemotherapy [1, 2]. In addition to a possible clinical benefit by downstaging the tumor before surgery, a great interest in neoadjuvant chemotherapy has been developed because it serves as an in vivo experiment for both patients and physicians to see whether or not the tumor responds to the given therapy. In a relevant number of patients the tumor completely disappears from breast and the axilla. It has been shown that this pathological complete response (pCR) is an excellent predictor of prognosis, especially in some molecular subgroups [3, 4]. In a pooled analysis, up to 35% of all patients with triple negative breast cancer (TNBC) achieved pCR after neoadjuvant chemotherapy, while in HER2-positive hormone receptor (HR)-negative patients up to 50% achieved pCR after chemotherapy and trastuzumab (TCH) therapy [3]. Much lower pCR rates are achieved in HRpositive, HER2-negative patients, with pCR rates as low as 8% for tumors with a grading of 1 or 2 and about 16% with a grading of 3 [3]. With regard to outcomes, the translation of pCR into a good prognosis is prominent for triple negative and HER2-positive patients; however, this is difficult to show for other subtypes, such as HR-positive patients with a grading of 1 and 2 [3]. In this issue of Breast Care, Gaß et al. [5] explore which HR-positive patients should receive adjuvant and neoadjuvant chemotherapy. The treatment of these patients is a challenge because they have a good prognosis but often do not respond to chemotherapy. Novel molecular tests might help to identify those patients who have an excellent prognosis and therefore do not need chemotherapy [6, 7]. The low response rates in HR-positive, HER2-negative patients has Published online: October 24, 2016

Abstract: Background: Ductal carcinoma in situ of the male breast is an unusual lesion and most often associated with invasive carcinoma. On rare occasions when the in situ component is present in pure form, histological grade is almost always low to intermediate. Imaging for these patients is difficult as gynecomastia is often present and can mask underlying calcifications or carcinoma. Case Report: We report a case of pure high-grade ductal carcinoma in situ of the male breast in a patient with clear nipple discharge. Breast mammography showed bilateral gynecomastia and benign calcifications. Subsequent breast ultrasound showed dilated ducts of the left breast, and a left breast ductogram showed filling defects suggestive of a papilloma. Excisional biopsy and subsequent mastectomy were consistent with high-grade ductal carcinoma in situ. Conclusion: Male breast cancer is uncommon and, although there is increasing awareness, it is less studied compared to female breast cancer. With a clinical history of nipple discharge of any kind, further evaluation with imaging should be considered. In males with gynecomastia, it is important to remember that ductal carcinoma in situ, even of high grade, is difficult to detect on mammography and may not be associated with suspicious calcifications.

Abstract: Purpose: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergon

Abstract: Background: The aim of this study was to characterize the signs of invasive lobular carcinoma of the breast on digital breast tomosynthesis (DBT) imaging. Patients and Methods: The study group included 23 women with pathologically proven invasive lobular carcinoma of the breast for whom both digital mammography (DM) and DBT images were available. The images were read jointly by 2 experienced breast radiologists. Findings were recorded according to the descriptors in the Breast Imaging and Reporting Data System lexicon and correlated with the detailed pathology results. Results: In 21 of the 23 patients, the combination of DM and DBT yielded pathologic findings (91%). Architectural distortions or spiculations were demonstrated in 87% of cases. The addition of DBT to DM improved lesion detection by more clearly depicting both the lesion margins and architectural distortions. Only 2 lesions were occult by both DM and DBT, including 1 lesion in a peripheral location that was not incorporated in the standard mediolateral oblique and craniocaudal views. Conclusion: DBT improves the detection of invasive lobular carcinoma lesions by more clearly depicting architectural distortions and spiculations.

Abstract: Despite the advancement of targeted therapies in metastatic breast cancer, chemotherapy is still of pivotal importance. The concept of dose density is known to increase the efficacy of chemotherapy. In metastatic disease, preservation of the quality of life is equally important. Because of this, weekly regimens are a cornerstone in metastatic disease. Taxanes like paclitaxel or nab-paclitaxel as well as antracyclines are often used in palliative treatment. Further advances to increase dose density have led to the concept of daily metronomic schedules with oral chemotherapeutic drugs like cyclophosphamide, capecitabine, or vinorelbine. Metronomic chemotherapy affects tumor angiogenesis and also weakens immunosuppressive regulatory T cells, promoting better control of tumor progression. Weekly or daily dose-dense regimens are a reasonable compromise between efficacy and toxicity to improve the therapeutic index. This is most important for the treatment of chronic disease where palliation and preservation of quality of life are vital.

Abstract: Background: Pyoderma gangrenosum (PG) is a rare cutaneous ulcerative disease that does not respond to antibiotics and worsens with surgical manipulation. This is the first report in the literature revealing that this disease complicates total microsurgical breast reconstruction associated with the transfer of free lymph nodes. Case Report: We report the case of a female patient who underwent left-breast microsurgical reconstruction with a deep inferior epigastric perforator (DIEP) flap and simultaneous transfer of vascularized free lymph nodes for the surgical treatment of secondary left upper-limb lymphedema, and who developed a severe PG of both the skin of the flap and the donor zone on postoperative day 7. After exclusion of other etiologies, treatment with high-dose corticosteroids and topical zinc sulfate was initiated. The flap was salvaged and breast cancer-related lymphedema (BCRL) surgery was definitively effective despite the PG. Conclusions: PG should be considered in the differential diagnosis of progressive cutaneous ulcers following surgical interventions, once infectious and ischemic etiologies have been excluded. Early initiation of immunosuppressive treatment can lead to preservation of the initial flap and function of the transferred lymph nodes in the case of microsurgical breast reconstruction with associated lymph node transfer.

Abstract: The Advanced Breast Cancer Third International Consensus Conference on the diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal, on November 5-7, 2015. This year's conference (ABC3) was focused on the treatment of metastatic breast cancer (stage IV), as it was 4 years ago at the first consensus meeting (ABC1). A matter of particular interest was the patients' perspective. Thus, patient-relevant issues were addressed by the consensus discussions, such as those on treatment goals, quality of life, care of long-term survivors ('survivorship issues'), and coping with disease-related symptoms and the side effects of treatment. Further important issues on the agenda were the use of standardized instruments for the assessment of individual treatment success ('patient-reported outcome measures') and the evaluation of the benefit of novel drugs (e.g. the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale). Diagnosis and treatment of inoperable locally advanced breast cancer had already been discussed 2 years earlier at the ABC2 Consensus and were not dealt with in the framework of this year's ABC3 Consensus. With regard to country-specific peculiarities, which unavoidably found their way into the ABC Consensus, a working group of German breast cancer experts commented on the voting results of the ABC panelists. As for the past consensus, the group specially considered the German guidelines for the diagnosis and treatment of breast cancer (AGO (Gyneco-Oncology Working Group), S3, DGHO (German Society of Hematology and Medical Oncology)) in order to adapt the ABC3 consensus for everyday therapy in Germany.

Abstract: Background: Neuroendocrine carcinoma is an uncommon histology for breast cancer. Case Report: Our patient underwent right qu

Abstract: Background: The axillary nodal status is essential to determine the stage of disease at diagnosis. Our aim was to prospectively assess the diagnostic accuracy of ultrasonography-guided fine-needle aspiration (US-FNA) for the detection of metastasis in axillary lymph nodes in patients with breast cancer (BC) and its impact on the therapeutic decision. Materials and Methods: Ultrasonography (US) was performed in 407 axillae of 396 patients who subsequently underwent surgery. US-FNA was conducted when lymph nodes were detected by US. Axillary dissection (AD) was performed when US-FNA was positive for metastasis. Patients with negative US-FNA and breast tumors of 30 mm in size were candidates for selective sentinel lymph node biopsy (SLNB). The anatomopathological results of AD or SLNB were used as reference tests. Results: Lymph nodes were detected by US in 207 (50.8%) axillae. Of these, US-FNA was performed on 180 (86.9%). 94 axillae (52.2%) were positive for carcinoma and 79 women received AD. US-FNA had 77.5% sensitivity, 100% specificity, 100% positive predictive value, 69.3% negative predictive value, and 85.1% diagnostic accuracy. US-FNA avoided SLNB in 18.1% of patients who underwent AD. Conclusions: Axillary US-FNA is an accurate technique in the staging of patients with BC. It allows reducing the number of SLNB and, when positive, offers a fast and useful tool.

Abstract: Endocrine therapy is the cornerstone in the treatment of hormone receptor-positive breast cancer. During the last decades, much has been learned about the subtle regulation of the cell cycle. In this tightly regulated network, cyclin-dependent kinases (CDKs) play a pivotal role. Especially CDK4/6 is the key regulator of the G1-S transition. Realizing its importance, specific inhibitors of CDK4/6 were developed. The drug most advanced in clinical development in this class is palbociclib (PD 0332991). This review highlights preclinical data and brings into focus early clinical trials that led to an accelerated approval by the US Food and Drug Administration (FDA) as first-line treatment in combination with letrozole in advanced hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Furthermore, ongoing clinical trials with palbociclib in advanced and in early breast cancer are outlined. In conclusion, inhibition of CDK4/6 using palbociclib in combination with endocrine therapy is an efficacious treatment option in hormone receptor-positive/HER2-negative advanced breast cancer. Ongoing clinical trials will show whether palbociclib is ready for prime time in early breast cancer.

Abstract: Introduction: Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of do

Abstract: Background: Circulating tumor cells (CTCs) are cells that detach from a primary tumor, circulate through the blood stream and lymphatic vessels, and are considered to be the main reason for remote metastasis. Due to their origin, tumor cells have different gene expression levels than the surrounding blood cells. Therefore, they might be detectable in blood samples from breast cancer patients by real-time quantitative polymerase chain reaction (RT-qPCR). Materials and Methods: Blood samples of healthy donors and adjuvant breast cancer patients were withdrawn and the cell fraction containing white blood cells and tumor cells was enriched by density gradient centrifugation. RNA was isolated and reverse transcribed to cDNA, which was then used in TaqMan real-time PCR against cytokeratin (CK)8, CK18 and CK19. 18S and GAPDH were used as controls. Results: All 3 CKs were, on average, found to be significantly higher expressed in adjuvant breast cancer samples compared to negative controls, probably due to the presence of CTCs. Unfortunately, gene expression levels could not be correlated to tumor characteristics. Conclusions: RT-qPCR could make up a new approach for the detection of CTCs from blood samples of breast cancer patients, but a correlation of the PCR data to gold standard methods in CTC detection would help to further improve the informative value of the qPCR results.

Abstract: Due to the enhanced understanding of molecular oncology and signaling pathways in breast cancer (BC), therapy management has undergone a major transformation, especially with the emergence of treatment tailored to individual disease characteristics. In the case of HER2-positive early or metastatic BC, targeted therapies are well established and remain a major focus of ongoing research. The introduction of anti-HER2 biologicals such as trastuzumab, pertuzumab, and T-DM1 has made targeted and personalized treatment possible and has clearly improved disease-free and overall survival in patients with HER2-positive BC. Moreover, neoadjuvant chemotherapy represents a well-established and often favored option for patients with operable BC and a clear indication for postoperative chemotherapy (such as HER2-positive BC). Other trials are trying to identify additional surrogate markers for therapy response and clinical outcome in the neoadjuvant setting and that way open up new perspectives with a possible de-escalation of classical treatment in favor of targeted therapy.

Abstract: Objective: We aimed at examining the potential benefits of blue dye in sentinel node biopsy (SNB) in comparison with its proven drawbacks. Patients and Methods: In 2007, 203 T1 primary breast carcinomas had been operated on in our institute. The patients had undergone a lumpectomy and SNB. Sentinel node (SN) detection was exclusively isotopic (ISO) in 77 patients and performed with blue dye combined with a radioactive isotope (COMBI) in 126 patients. We compared the number of SNs and the rate of SN positivity in both groups. Results: The detection rate was 99% in both groups: 76/77 in the ISO group and 125/126 in the COMBI group. The mean number of SNs was 2.14 and 1.91 in the ISO group and the COMBI group, respectively (difference not significant (NS)). SN positivity was found in 26.1% and 24.6% in the ISO group and the COMBI group, respectively (NS). Only 1 SN had been removed in 26% of the patients in the ISO group versus 45.2% of the patients in the COMBI group (p = 0.004). No significant differences were observed in the tumor characteristics. Conclusion: The systematic use of patent blue dye combined with isotopic detection does not appear to increase the overall performance of the SNB technique in this retrospective study.

Abstract: Background: This study aimed to identify the association of local surgery of the primary tumor in metastatic breast cancer (MBC) patients with overall survival (O

Abstract: Background: The natural course of traditionally prognostically unfavorable human epidermal growth factor receptor 2 (HER2)-positive breast cancer has been changed by anti-HER2 therapy. It is not clear whether the prognosis for HER2-positive patients treated with adjuvant trastuzumab differs from that of HER2-negative patients. Methods: We performed a retrospective study including patients with lymph node-negative invasive breast cancer treated at our institution in the period 2000-2009. Disease-free (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The Cox proportional hazards model was applied to control for other clinically important variables. Results: Median follow-up was 90-109 months. The 5-year DFS rates for HER2-negative patients, HER2-positive patients without adjuvant trastuzumab and trastuzumab-treated HER2-positive patients were 88.1% (95% confidence interval (CI) 85.6-90.6%), 73.1% (95% CI 64.3-81.9%) and 90.7% (95% CI 83.1-98.3%), respectively. No significant difference in DFS was observed between trastuzumab-treated HER2-positive patients and HER2-negative patients in multivariate analysis (hazard ratio 1.15; 95% CI 0.53-2.46; p = 0.728). There were no differences in OS among the 3 groups. Conclusion: Based on our results, the negative prognostic effect of HER2 positivity seen before targeted anti-HER2 treatment has completely disappeared in the era of routine trastuzumab administration in the adjuvant setting.