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Breast cancer is a major threat worldwide. Hibiscus sabdariffa is widely consumed as beverage in sub-Saharan Africa for its anticancer potential. The present study therefore aimed at scientifically verifying its anticancer effect in rats. For this, 48 Wistar rats (∼55 days) were treated either with tamoxifen at 3.3 mg/kg BW (standard) or with a decoction of H. sabdariffa (125, 250, and 500 mg/kg BW) or distilled water (vehicle). Breast cancer was induced by a single dose of 50 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA). At the end of the 21 weeks of treatment, the tumor incidence, tumor morphology, histopathology, as well as some biochemical parameters in the tumors were assessed. As a result, 86% of DMBA's rats developed mammary tumors. The H. sabdariffa extract (125 and 250 mg/kg) reduced tumor incidence by 63% and 75%, respectively; inhibited tumor burden by 84.86% and 38.78%, respectively, and decreased tumor volume by more than 72% compared to the DMBA group. It also protected rats against DMBA-induced diffuse breast neoplasia, and the optimal effect was recorded at 125 mg/kg. Furthermore, it significantly increases the SOD activity and decreases the MDA level. In summary, H. sabdariffa has antibreast tumor and antioxidant properties in rats, which could justify its common use to treat cancer. [ABSTRACT FROM AUTHOR]

In the recent past, DCIS was a rare diagnosis established by biopsy of palpable breast masses or nipple changes. Mammography increased the frequency of a DCIS diagnosis by 20 × resulting in a tsunami of small circa 10 mm lesions detected only by mammography. The impact of pathologic technique in examining and characterizing such lesions is reviewed, and the development of algorithms incorporating prognostic factors and histology based on serial sequential processing techniques are described and contrasted with those which relied on tissue sampling. The development of the initial clinical trails of irradiation all demonstrated the significant benefit of irradiation but none could identify subsets with a more favorable outcome. The latter was precluded by their common practice of tissue sampling: Size could not be calculated and margin width and microinvasion could not be reliable demonstrated. Multigene signature assays are increasingly being utilized, most prominently Oncotype DCIS. However, these assays must be interpreted in conjunction with the limitations set forth in the validating studies—in the case of Oncotype DCIS—the size, margin width, and grade which defined the baseline study (E5194). Tamoxifen and other anti‐hormonal agents (aromatase inhibitor therapy) have been shown to have a limited impact on ipsilateral recurrence which makes their use given their morbidities problematic. Such interventions do impact the frequency of contralateral occult in situ and invasive lesions. In the one study which permitted a comparison of local recurrence in irradiated vs nonirradiated breast, there was no added benefit of Tamoxifen in irradiated breasts. Some are attempting to identify a low‐risk subset of DCIS which can be treated without surgical re‐excision for margins or adjuvant irradiation. These studies are in progress but surrogates identified within the Van Nuys prospective series defined by grade and inadequate margins (≤ 1 mm) would suggest a significant recurrence and progression rate. DCIS remains a work in progress both in terms of classification and treatment. However, limited our progress in these areas we have certainly advanced from the oft‐proclaimed mantra: "Radiation and Tamoxifen are standard of care." [ABSTRACT FROM AUTHOR]

Highlight the challenges associated with managing breast cancer in female‐to‐male (FtM) transgender individuals. This is a rare entity, requiring nuanced decision‐making regarding surgery as well as adjuvant therapies given the unique hormonal environment seen in individuals taking exogenous androgen as part of their gender identity. Contemporary case report derived from our clinical experience. Discussion focuses on a brief summation of all known cases of female‐to‐male breast cancer in FtM individuals described in the literature. A 48‐year‐old FtM transgender individual on exogenous testosterone for 19 years with stage IIA (pT1cN1M0), ER+(8/8), PR+(8/8), Androgen Receptor(AR)+(5%‐8%), Her‐2‐negative invasive ductal carcinoma of the breast. Due to AR positivity in tumor, cessation of testosterone was chosen after careful consideration of potential ramifications from both a cancer treatment as well as gender identity standpoint. Endocrinology consultation reassured the patient that identity affirming changes of facial hair growth and voice depth would persist after cessation of testosterone. Patient did not wish to undergo chemotherapy and as such was treated with combination of radiation to the axilla, adjuvant Anastrozole and testosterone cessation. Although breast cancer is rare in FtM transgender individuals, it can occur. Many FtM individuals take exogenous testosterone. It is important to test the tumor for the androgen receptor as this may have important implications for both gender identity and treatment. Additionally, the mastectomy commonly performed for "top" surgery in this population is not adequate for oncologic control by itself and at present there is no guidance regarding postsurgical screening in this population, especially in those individuals with a strong family history of breast cancer. [ABSTRACT FROM AUTHOR]

The article discusses early relapse of inflammatory breast carcinoma treated with lapatinib and capecitabine. Topics include Trastuzumab was given every three weeks for a complete year; Compared with capecitabine alone, lapatinib in combination with capecitabine increases time to progression (TTP) in patients who have progressed after/on trastuzumab; and lapatinib has shown remarkable activity in IBC in two phase II trials.

HER2 is overexpressed in 20% of invasive breast cancers (BCs) and correlates with a more aggressive disease. Until the advent of targeted agents, HER2 was associated with worse outcomes. Rationally designed HER2-targeted agents have been developed and introduced into clinical practice for women with HER2-amplified BC, improving disease-free and overall survival for primary and metastatic tumors. Trastuzumab, a recombinant humanized anti-HER2 monoclonal antibody, combined with chemotherapy, remains the standard of care for patients with HER2-positive BCs. However, many patients do not respond to this agent, whereas newer drugs have proven to be efficacious in clinical trials. The identification of biomarkers that select sensitive tumors and patients who will benefit from these new agents would help the incorporation of these therapies, limiting the risk of side effects and overtreatment and improving the outcomes of all patients with early-stage HER2-positive BC. We review the mechanisms of action of HER2-targeting agents, focusing on the involvement of the immune system and related predictive biomarkers. [ABSTRACT FROM AUTHOR]

Background. Breast cancer remains the leading cause of cancer-related mortality worldwide. It has been indicated that human papillomaviruses 16 (HPV16) might participate in the pathogenesis and development of breast cancer. However, the detected rate of HPV16 varies with region. We will investigate HPV16 E6 expression in North China and explore the effects and mechanism of HPV16 E6 on breast cancer proliferation in this study. Methods. The expressions of HPV16 E6 and COX-2 in paraffin-embedded tissues of the invasive ductal breast cancer were detected by qPCR and IHC. The effects of HPV16 E6 on breast cancer proliferation were determined by function studies. The mechanism of HPV16 E6 in promoting breast cancer proliferation was explored by Western blot and Dual-Luciferase Reporter Assay. Results. HPV16 E6 was positive in 28% invasive ductal breast carcinoma in North China; HPV16 E6 promoted breast cancer proliferation. Inhibition of COX-2 by siCOX-2 or Celecoxib attenuated the proliferation of breast cancer cells with HPV16 E6 expression; and the upregulation of COX-2 could be suppressed by the inhibition of NF-κB activity. Conclusion. HPV16 E6 promotes breast cancer proliferation by activation of NF-κB signaling pathway and increase of COX-2 expression. COX-2 will be a potential target for HPV16 E6-associated breast cancer. [ABSTRACT FROM AUTHOR]

To provide reference data, we retrospectively investigated the effects of neoadjuvant chemotherapy (NAC) on 119 patients with HER-2+ locally advanced breast cancer, treated from November 2010 to July 2016, with respect to influencing factors and survival. They were divided into the pathological complete response (pCR; n=15; 12.6%) and non-pCR (n=104; 87.4%) groups. We used Χ2 and logistic tests to the analyze effect and influencing factors. Survival rate was analyzed by the Kaplan-Meier method and Log-rank test. We lost 12 patients (including 1 pCR patient) and followed 107 patients, of whom 31 (all in the non-pCR group) had local recurrences or distant metastasis. The two groups significantly differed in 3-year disease-free survival (pCR group: 100%; non-pCR group: 59.0%; P=0.039); pCR was significantly affected by histological grade, PR status, Ki67 index, primary tumor size, clinical staging, and number of trastuzumab cycles. The model was tested, and the difference was statistically significant (Χ2 = 31.938, P=0.032). Patients with HER-2+ locally advanced breast cancer with pCR responses to NAC have improved prognoses. Patients without pCR have increased risk for relapse. The use of a combination of NAC, such as trastuzumab and chemotherapy, and more cycles should be considered to increase the likelihood of pCR. [ABSTRACT FROM AUTHOR]

Lipegfilgrastim is a long-acting, once-per-cycle, glycopegylated recombinant granulocyte colony-stimulating factor (G-CSF) used to prevent neutropenia in patients receiving myelosuppressive chemotherapy. This integrated analysis examined the immunogenicity of lipegfilgrastim and its potential clinical impact in two double-blind randomized studies (phases II and III) of patients with breast cancer receiving chemotherapy. Serum samples were analyzed using sequential assays for screening, confirmation, antibody titer, and characterization of antidrug antibodies (ADA). Neutropenia-related efficacy measures were reviewed for each ADA-positive patient. Among 255 patients receiving lipegfilgrastim (154 in phase II, 101 in phase III) and 155 patients receiving pegfilgrastim (54 in phase II, 101 in phase III), the incidence of treatment-emergent ADA was low and similar between the lipegfilgrastim (phase II: 1.3%; phase III: 1.0%) and pegfilgrastim (phase II: 1.9%; phase III: 1.0%) arms. None of the treatment-emergent ADA-positive samples exhibited neutralizing activity against lipegfilgrastim, pegfilgrastim, or glycosylated G-CSF in a cell-based neutralizing antibody assay. No changes were observed in neutropenia-related efficacy measures among ADA-positive patients, and no treatment-related hypersensitivity or anaphylaxis occurred. These results indicate that there is no apparent impact of ADA on lipegfilgrastim efficacy and safety. [ABSTRACT FROM AUTHOR]

The authors provide a perspective on the rapidly evolving field of prognostic analyses designed to quantify the risk of local recurrence in conservatively treated ductal carcinoma in situ (DCIS). These include morphologic features variously defined, nomograms, algorithms and multi-gene expression assays-all of which have completed against the perceived conclusions of the randomized trials of irradiation and Tamoxifen for DCIS: 'all subsets benefit'. At present the majority of newly diagnosed DCIS can be adequately treated with surgery alone. A number will require irradiation to achieve acceptable local control, and a minority will require mastectomy regardless of adjuvant treatments. Differences in the definition of prognostic factors and in the methods used to establish them is a major reason for the lack of consensus in treatment recommendation. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the possible use of mouse double-minute 2 (MDM2) molecular imaging to predict chemotherapeutic sensitivity in breast cancer xenografts (BCXs). MCF-7 cells were transfected with MDM2 antisense oligonucleo-tides (ASONs), and MDM2 expression levels were determined by Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in MCF-7 cells transfected with ASONs and treated with paclitaxel. BCXs were established in nude mice by injection of ASONs, and tumor volumes were measured after paclitaxel treatment. MDM2 ASONs were labeled with 99mTc to generate an MDM2 molecular probe, and MDM2 expression levels were evaluated by imaging and Western blotting. MDM2 ASONs downregulated MDM2 expression in a dose-dependent manner and increased the rate of paclitaxel-induced cell growth inhibition. Imaging of tumors revealed significant differences in the tumor to skeletal muscle (T/M) ratio between groups. Tumor MDM2 protein expression was correlated with T/M ratios at 4 hours (R = .880) and 10 hours (R = .886). The effect of paclitaxel varied among nude mice bearing BCXs with different concentrations of ASONs, as shown by differences in tumor growth. MDM2 molecular imaging could be a promising method for predicting the sensitivity of BCXs to chemotherapy. [ABSTRACT FROM AUTHOR]

Hypersecretion of PTHrP is a relatively common cause of malignancy-related hypercalcemia. However, there is only one case report of letrozole induced hypercalcemia. A 52-year-old female patient was referred to our clinic because of the recent discovery of hypercalcemia (11.0 mg/dL). The patient had a history of left breast carcinoma. She had started a course of letrozole (aromatase inhibitor; 2.5 mg dose/day) ten months earlier. Patient's parathyroid hormone-related protein levels were normal and a bone scintigram revealed no evidence of skeletal metastasis. Other potential causes of high calcium levels were ruled out. We recognized that, when letrozole was taken at one dose daily (2.5 mg), she had recurrent hypercalcemia. Our experience suggests that letrozole may precipitate hypercalcemia in a patient with breast cancer. [ABSTRACT FROM AUTHOR]

The article present case study of a 50-year-old female patient presented in June 2015 with complaints of lump in left breast for 1 month duration. Topic include Mammography revealed mass at inferior medial segment of left breast, involve fine needle aspiration cytology and biopsy were suggestive of ductal carcinoma.

A major problem in the treatment of breast cancer is the development of resistance to chemotherapeutic agents. Although the role of multidrug resistance 1 (MDR1) and multidrug resistance associated protein 1 (MRP1) in inducing drug resistance in many cancers has been widely investigated the clinical significance of expression of these genes in breast cancer remains unclear and the data is still controversial. We investigated the expression of MDR1 and MRP1 in breast cancer patients as well as the possible correlation between MDR1 and MRP1 and clinical response to chemotherapy. In the present study, MDR1 and MRP1 gene expression were investigated by real time reverse transcription polymerase chain reaction (RT-PCR) assay in 54 breast cancer tumors and in corresponding adjacent normal tissues before neoadjuvant chemotherapy. The expression level of MDR1 and MRP1 were significantly higher in breast tumors than normal breast tissues. Although a significant relationship was found between the MRP1 expression and response to treatment no association was observed between MDR1 expression and response to treatment. MDR1 and MRP1 expression levels have been shown to be independent of tumor size, histological grade and the status of progesterone or estrogen receptor. [ABSTRACT FROM AUTHOR]

A 72-year-old woman underwent a mastectomy with one-stage breast reconstruction using silicone implant for right breast cancer. Postoperatively, she had received adjuvant chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC regimen). She was admitted for febrile neutropenia after the third course of chemotherapy. She remained febrile for a week, and she complained of dyspnea on hospital day 8. Computed tomography scan demonstrated widespread patchy ground glass changes in both lungs and serum (1 → 3)- β-D-glucan was elevated to 20 pg/mL. Oral trimethoprim-sulfamethoxazole was started on the strong clinical suspicion of PCP, and the patient subsequently made a rapid recovery from fever and dyspnea. [ABSTRACT FROM AUTHOR]

Myoepithelial carcinoma (malignant myoepithelioma) of the breast is a rare tumor, for which only a limited number of reports have been published. Most of the reports emphasized diagnosis and pathology but not biological behavior and treatment. We report a 61-year-old patient with breast myoepithelial carcinoma who developed locoregional and distant metastases and received many chemotherapy regimens. She presented with an elastic hard mass of the left breast. Breast conserving surgery was performed as part of both diagnosis and treatment. From the results of histological and immunohistochemical examinations, this case was considered to be a myoepithelial carcinoma. Fifteen months after the completion of adjuvant radiotherapy, distant metastasis of the left parasternal lymph node metastasis developed. She was treated by further excision and received a total of four regimens of chemotherapy including a combination of doxorubicin and cyclophosphamide. She received chemotherapy for 20 months after the diagnosis of metastasis. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various articles within the issue on topics including the use of exemestane in postmenopausal women who have undergone mastectomy for ductal carcinoma in situ (DCIS) and the systematic review of the available literature investigating molecular factors used to predict risk in patients with DCIS.

For postmenopausal women with ductal carcinoma in situ (DCIS) where optimal local control or patient preference results in mastectomy, despite substantial risk of contralateral invasive breast cancer, tamoxifen is uncommonly prescribed based on unfavorable risk-benefit consideration. In the National Cancer Institute of Canada Clinical Trial Group (NCIC CTG) MAP.3 primary prevention trial, in postmenopausal women exemestane reduced invasive breast cancer incidence by 65% without increasing life-threatening side effects. In adjuvant breast cancer trials, the aromatase inhibitor exemestane as well as anastrozole and letrozole have all reduced new contralateral breast cancer incidence. Thus, aromatase inhibitors, and perhaps particularly exemestane, provide an option to address the risk of contralateral breast cancer in postmenopausal women with DCIS managed with mastectomy. [ABSTRACT FROM AUTHOR]

Ductal carcinoma in situ (DCIS) describes a wide spectrum of non-invasive tumors which carry a significant risk of invasive relapse, thus prevention of local recurrence is vital. For appropriate patients with limited disease, management with breast conserving surgery (BCS) followed by whole-breast radiation (RT) is supported by multiple Phase III studies, but mastectomy may be appropriate in selected patients. Omission of RT may also be reasonable in some patients, though which criteria are to be utilized remain unclear, and the existing data are contradictory with limited follow-up. Various RT techniques such as boost to the tumor bed, partial breast radiation or hypofractionated, whole-breast RT are increasingly utilized but the data to support their use specifically in DCIS is limited. Tamoxifen also increases local control for ER + DCIS, adding to the complexity of the local treatment management. This article reviews the existing scientific evidence, the controversies surrounding local management, and clinical guidelines for DCIS based on the group consensus by the ACR Breast Expert Panel. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

About two-thirds of all breast cancer patients are treated with adjuvant hormonal therapy. Side effects of tamoxifen and their effects on physical, emotional and social functioning have been shown to impair the quality of life. Aim of this paper was to evaluate the side effects and level of influence on the physical, emotional and social functioning caused by tamoxifen treatment. For assessment of quality of life an own questionnaire was designed. Between January 2001 and December 2003, 136 women with breast cancer and adjuvant tamoxifen therapy were included in this study. Data of side effects, physical and mental health and patients’ self-evaluation identified detrimental effects on patients’ quality of life. Prevalence and severity of symptoms were not influenced by length of tamoxifen treatment. Patients were damaged in their constitution in respect to previous chemotherapy and pre-existing diseases; no influence was found by age or histopathological tumour characteristics. Our survey determines that breast cancer patients experience significant influence on quality of life by the negative impact on the physical, emotional and social functioning caused by tamoxifen treatment. Explicit attention to changes in quality of life should be considered as part of the standard care for women receiving adjuvant tamoxifen treatment. [ABSTRACT FROM AUTHOR]

The article aberrant lymphatic drainage in relapsed breast carcinoma where the usefulness of the lymphoscintigraphy. Topics include finally, the two right breast tumors were staged as pT1C‐pN0‐ Mx, and the patient received adjuvant treatment with Trastuzumab and Tamoxifen; it is possible that the extraaxillary or contralateral axillary lymph nodes correspond to direct lymphatic migration from the primary tumor; and which could be important in prognostic and therapeutic decisions.

A case study is presented of a 47‐year‐old woman numerous bony metastases. Plain chest radiographs revealed findings consistent with bilateral pulmonary interstitial and airspace opacification with lower lobe predominance, and computed tomography chest angiography was obtained to exclude a pulmonary embolism. She was reffered for everolimus‐induced pneumonitis.

A letter to the editor is presented commenting on pharmacokinetics of Trastuzumab, a humanized monoclonal antibody, in haemodialysis.

Although rare, clinicians and patients must be aware that therapy related malignancies, specifically acute myeloid leukemia (AML), can occur asa complication of adjuvant chemotherapy for breast cancer. Vigilance for signs and symptoms is appropriate. AML with t (8;16) is a specific translocation leading to formation of a fusion protein (MYST3/CREBBP). The MYST3/CREBBP AML tends to develop within 2 years of adjuvant chemotherapy, especially for breast cancer, without preceding myelodysplasia. It usually presents with disseminated intravascular coagulation and osteolytic lesions and has a poor prognosis despite aggressive resuscitation and therapy. With the increasing use of adjuvant chemotherapy for breast cancer, we are seeing a definite increase in the incidence of therapy related myelodysplastic syndromes and AML. One must keep this complication in mind while counseling and following up breast cancer patients who have received adjuvant chemotherapy. New osteolytic bone lesions in a patient with history of breast cancer do not necessarily mean metastatic disease and should be fully evaluated. [ABSTRACT FROM AUTHOR]

The article discusses the molecular analysis of pleomorphic ductal carcinoma of the breast. Topics discussed include the calculation of total mutational load and microsatellite instability, measuring Copy number variations for DNA sequencing, and the use of immunohistochemistry for gene expression. The author states the need for predictive biomarker and theranostics to treat rare breast cancer subtype.

A 64-year-old man with moderate intellectual disability developed a large right breast carcinoma with lymph node metastases. Cancer treatment is often difficult in persons with intellectual disability. However, the patient could be treated according to the current protocols with surgery, chemotherapy, and radiotherapy. He is alive and in good health two years after discovery of his tumor. Although breast cancer is estimated as frequent in women with intellectual disability as it is in nondisabled women, our patient is the second man with intellectual disability reported with a breast carcinoma. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 48-year-old postmenopausal woman who experienced chest pain, and perspiration for 30 minutes. The medical history of the patient revealed that she was diagnosed with infiltrative ductal carcinoma of the left breast and underwent left sided modified radical mastectomy wherein she received an aromatase inhibitor (AI) of letrozol. She was examined using electrocardiography and revealed an acute anterior ST segment elevation myocardial infarction (STEMI).