Breast

Post-surgical pyoderma gangrenosum of the breast: needs for early diagnosis and right therapy Abstract Post-surgical pyoderma gangrenosum (PSPG) of the breast is a rare dermatosis that worsens surgical manipulation, with a chronical relapsing course. Diagnosis is mostly clinical and made by exclusion after the failure of antibiotic therapies and surgical debridement, while the mainstay of therapy is corticosteroid-based. Here we report a case of PSPG of the breast in a young woman with breast cancer, to emphasize the needs of an early and accurate diagnosis, to guarantee the most efficacious treatment and to avoid life-threatening complications.

Apocrine papillary lesion: comparison of pathological findings from 22 years previously and the present Abstract Apocrine papillary lesion (APL) is difficult to diagnose as benign or malignant. We experienced an APL remaining in the body for 22 years. We present a case of a 71-year-old woman who had undergone excisional biopsy 22 years previously at the first hospital that she visited. 1 year previously, she had undergone fine-needle aspiration cytology at a second hospital, and the lesion was diagnosed as potentially malignant. She underwent core-needle biopsy at a third hospital, but whether the lesion was benign or malignant could not be definitively diagnosed. We performed right mastectomy and sentinel lymph-node biopsy, because her tumor was suspected to be malignant based on imaging means, and malignancy could not be ruled out on either biopsy or cytology. The histopathological diagnosis was tiny foci of apocrine proliferative lesion with massive hemorrhagic necrosis and no tumor metastasis in two sentinel lymph nodes. Retrospectively, we compared all of the patient’s previous specimens with the present ones, and applied the recent pathological diagnostic criteria. Although the biopsy specimen excised 22 years ago suggested an encapsulated apocrine papillary carcinoma or a papilloma with apocrine ductal carcinoma in situ, neither infiltration nor metastasis has occurred. Furthermore, neither the pathological findings nor the clinical behavior has changed over time.

Clinical application of ceramide in cancer treatment Abstract Development of innovative strategies for cancer treatment is a pressing public health issue. Despite recent advances, the mechanisms of cancer progression and the resistance to cancer treatment have not been fully elucidated. Sphingolipids, including ceramide and sphingoshin-1-phosphate, are bioactive mediators that regulate cancer cell death and survival through the dynamic balance of what has been termed the ‘sphingolipid rheostat’. Specifically, ceramide, which acts as the central hub of sphingolipid metabolism, is generated via three major pathways by many stressors, including anti-cancer treatments, environmental stresses, and cytokines. We have previously shown in breast cancer patients that elevated ceramide correlated with less aggressive cancer phenotypes, leading to a prognostic impact. Recent studies showed that ceramide have the possibility of becoming the reinforcing agent of cancer treatment as well as other roles such as nanoparticles and diagnostic biomarker. We review ceramide as one of the key molecules to investigate in overcoming resistance to current drug therapies and in becoming one of the newest cancer treatments.

Comparison of the efficacy of trastuzumab emtansine between patients with metastatic human epidermal growth factor receptor 2-positive breast cancers previously treated with combination trastuzumab and pertuzumab and with trastuzumab only in Japanese population Abstract Background Trastuzumab emtansine (T-DM1) has been approved since 2013 for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who had received trastuzumab (Tmab) and taxane. However, no clinical trial has evaluated the efficacy of T-DM1 in those who have previously received pertuzumab (Pmab). This study aimed to compare the efficacy of T-DM1 between patients who had received Tmab and Pmab and those who had received Tmab only in Japanese population. Methods We identified all patients with HER2-positive MBC who received T-DM1 between April 1, 2014 and February 28, 2017 in our institution. The patients were divided into the Tmab group (i.e., those who received only Tmab before T-DM1 treatment) and the Tmab/Pmab group (i.e., those who received Tmab and Pmab before T-DM1 treatment), and progression-free survival (PFS) and best response were compared between the two groups. Results A total of 42 patients were enrolled for outcome analysis. The median follow-up period was 4.8 months, and the median number of prior chemotherapy regimens for metastatic disease before T-DM1 was 1 (range 1–2) in the Tmab/Pmab group and 2 (range 0–6) in the Tmab group. The median PFS was 2.8 months in the Tmab/Pmab group (95% confidence interval [CI] 1.7–4.8 months) and 7.8 months in the Tmab group (95% CI 5.5–15.9 months) (p = 0.0030). The best response was lower in the Tmab/Pmab group (11.1% vs. 25.0%). Conclusions Patients with HER2-positive MBC who received Tmab and Pmab treatment before T-DM1 have fewer benefits from T-DM1.

Paving the way for changing perceptions in breast surgery: a systematic literature review focused on oncological and aesthetic outcomes of oncoplastic surgery for breast cancer Abstract Background The emphasis on aesthetic outcomes and quality of life after breast cancer surgery has motivated breast surgeons to develop oncoplastic breast conserving surgery (OPS). Training programs are still rare in most countries, and there is little standardization, which challenges the scientific evaluation of these techniques. This systematic review aims to assess oncological and cosmetic outcomes of OPS. Methods After a strict selection process with precise inclusion and exclusion criteria, oncologic and aesthetic outcomes of oncoplastic surgery were searched, using the MEDLINE database up to September 30th, 2017. Available published literature was classified in levels of evidence. After a thorough screening process, only studies with the best level of evidence were included on selection. Systematic reviews and meta-analyses were not included for methodological reasons. Results Titles and abstracts of 2.854 citations were identified and after screening 15 prospective studies including 1.391 patients were reviewed and scored in detail. Local relapse was found in 2.8% of cases with a wide range of follow-up (from 6 to 74 months). Close margins were retrieved in 11% of cases and positive margins in 9.4% of cases. Mastectomy was implemented in 6.9% of breast cancer patients to whom OPS was performed. Good cosmetic outcomes were detected in 90.2% of patients undergoing OPS, leaving open issues for who should perform cosmetic evaluation and which method should be used. Conclusion Tumor margins, mastectomy rates, and cosmetic outcomes of OPS have to be further improved by standardizing various aspects of OPS. Research efforts should focus on level I evidence assessing both oncological and aesthetic outcomes of OPS and survival rates.

Reinterpretation of BRCA1 and BRCA2 variants of uncertain significance in patients with hereditary breast/ovarian cancer using the ACMG/AMP 2015 guidelines Abstract Background Although BRCA1 or BRCA2 (BRCA1/2) genetic testing plays an important role in determining treatment modalities in patients with hereditary breast and ovarian cancer, sequence variants with unknown clinical significance or variant of uncertain significance (VUS) have limited use in medical decision-making. With vast quantities of gene-related data being updated, the clinical significance of VUS may change over time. We reinterpreted the sequence variant previously reported as BRCA1/2 VUS results in patients with breast or ovarian cancer and assessed whether the clinical significance of VUS was changed. Methods We retrospectively reviewed medical records of 423 breast or ovarian cancer patients who underwent BRCA1/2 genetic testing from 2010 to 2017. The VUSs in BRCA1/2 were reanalyzed using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines (ACMG/AMP 2015 guidelines) and the VUS was reclassified into five categories: “pathogenic”, “likely pathogenic”, “VUS”, “likely benign”, and “benign”. Results A total of 75 patients (48 sequence types of VUS) were identified as carrying either one or more VUS in BRCA1/2. Among the 75 patients, two patients (2.7%) were reclassified as “likely pathogenic”, 30 patients (40.0%) were reclassified as either “benign” or “likely benign”, and the remaining 43 patients (57.3%) were still classified as VUS category. Conclusions Since the clinical significance of VUS in BRCA1/2 may vary from time to time, reinterpretation of the VUS results could contribute to clinical decision-making.

Breast cancer incidence, mortality and mortality-to-incidence ratio (MIR) are associated with human development, 1990–2016: evidence from Global Burden of Disease Study 2016 Abstract Objective To examine breast cancer burden in females using incidence, mortality and mortality-to-incidence ratio (MIR) and its association with human development. Methods We employ the data of breast cancer in females from the Global Burden of Disease 2016 study for the period 1990 to 2016 for 102 countries. Human development is measured using the human development index (HDI). 5-year survival rate of breast cancer is proxied using the mortality-to-incidence ratio (MIR). Findings Globally, breast cancer has claimed 535341 female lives and 1.7 million incident cases had surfaced in 2016. High incidence rates were observed in very high HDI countries led by the Netherlands (117.2/100,000), whereas the mortality rate was high in low/medium HDI countries led by Afghanistan (35.4/100,000). Breast cancer incidence has more than doubled in 60/102 countries, whereas deaths have doubled in 43/102 countries. Globally, breast cancer MIR decreased from 0.41 to 0.32 over 1990–2016 and displayed negative gradient with HDI (r = − 0.87), indicating a low 5-year survival in less developed countries. Conclusion Heterogeneity in breast cancer burden, as per human development, and increasing breast cancer incidence and low survival rates, indicated by MIR, call for broader human development, improving breast cancer awareness, and cost-effective screening and treatment in less developed countries.

Cancer stem-like properties of hormonal therapy-resistant breast cancer cells Abstract Background Presently, hormonal therapy targeting estrogen receptors is the most effective treatment available for luminal breast cancer. However, many patients relapse after the therapy. It has been suggested that cancer stem-like cells are involved with hormonal therapy resistance; in the present study, we evaluated this hypothesis. Methods In the present study, we used our previously established hormonal therapy-resistant cell lines, including aromatase inhibitor (AI)-resistant cells (Type 1 and Type 2) and fulvestrant-resistant cells (MFR). Results AI-resistant cell lines expressing ER (Type 1 V1 and V2) showed high cancer stemness in terms of their CD44/CD24 expression and side populations, which were stimulated by the addition of estrogen and inhibited by fulvestrant. However, ALDH activity was lower than in the ER-negative resistant cells, suggesting that the stemness of luminal cells is distinct from that of basal-like breast cancer cells. The migration and invasion activity of the ER-positive Type 1 V1 and V2 cells were higher than in the ER-negative cell lines, Type 2 and MFR. Conclusions Fractionation of parental cells based on CD44/CD24 expression and colony formation assay indicated that CD44+/CD24+ cells might be the origin of hormonal therapy-resistant cells. This population reconstituted various other subpopulations under estrogen deprivation. These results indicate that hormonal therapy resistance is closely related to the cancer stem cell-like properties of luminal breast cancer.

URG4 expression in invasive breast carcinoma and its relation to clinicopathological characteristics Abstract Background Upregulated gene 4 (URG4) is a recently described oncogene that upregulates cell proliferation. Its overexpression has been identified in many malignancies, and it is thought to be related to tumour progression, angiogenesis, metastasis and the recurrence of many cancers. This is the first study to show its expression in breast cancer patients and its association with clinicopathological characteristics in these patients. Methods Fifty invasive ductal breast carcinoma cases and 25 control cases were included in the study. Tumourous tissues and control tissues were assessed molecularly for quantification of mRNA expression of URG4 and immunohistochemically for protein expression of URG4. Results The mean ages of the patients and controls were 54.3 ± 11.3 and 38.9 ± 9.7 years, respectively. The expression levels of URG4 mRNA in tumour tissues were higher compared to control breast tissues (p = 0.023). An immunohistochemical assessment suggested that URG4 is strongly expressed in normal breast tissues and lower-grade (grades I and II) ductal carcinomas of the breast, but it is weakly expressed in high-grade (grade III) ductal breast carcinomas. Additionally, the immunohistochemical and molecular expression results of URG4 were relevant to most prognostic parameters (tumour size, oestrogen and progesterone receptor status, HER2 status and Ki67 proliferative index) for breast cancer. However, unlike the immunohistochemical studies, the molecular studies revealed that there was no significant difference in URG4 expression for different grades of tumour tissues. Conclusion The literature data suggest that URG4 overexpression is associated with poor prognosis in many types of cancer. Conversely, our results in breast cancer specimens indicate that URG4 overexpression in breast ductal carcinomas is significantly associated with good prognostic parameters. Nevertheless, these preliminary findings should be confirmed by further studies.

Quantitative assessment and risk factors for chest wall deformity resulting from tissue expansion for breast reconstruction Abstract Background Chest wall deformity after tissue expansion for breast reconstruction is less recognized than complications such as infection, hematoma, skin necrosis and capsular contracture. However, the condition should not be discounted because pain, rib fracture and dyspnea may occur in severe cases. The aim of this study is to evaluate the extent of chest wall deformity quantitatively using computed tomography (CT) and to identify risk factors for this condition after tissue expansion. Methods The subjects were 34 patients who underwent unilateral two-stage reconstruction and were examined by multidetector-row CT before expander surgery and during maximal tissue expansion. Chest wall deformity was assessed quantitatively using the Chest Wall Deformity Index (CWDI), which was measured before expander surgery (pre-CWDI) and during maximal tissue expansion (post-CWDI). Post minus pre (post−pre) CWDI was used as the index of chest wall deformity in the assessment of risk factors. Result Post-CWDI was significantly higher than pre-CWDI (3.66 ± 3.23% vs. 0.03 ± 2.74%, P < 0.001 by paired t test), showing that chest wall deformity occurred after maximum expansion. In a multiple linear regression model, capsular contracture emerged as a significant predictor of increased post−pre CWDI (P = 0.003). BMI was a significant predictor of decreased post−pre CWDI (P = 0.003), but this result may have been due to the measurement method. Conclusions Our findings suggest that chest wall deformity is common after maximum tissue expansion for breast reconstruction. Awareness of the possibility of chest wall deformity during tissue expansion is important, particularly in cases with capsular contracture.