Actinomycosis; Malignancy; Breast; Cytology
Breast cancer; Treatment recommendations; Surgery; Adjuvant treatment
The efficacy of chemotherapy depends on the level of risk of the individual patient. Because of this, careful estimation of the risk level is mandatory. In addition to well-established clinicopathological factors, validated gene expression signatures might be useful in selected patients if all other criteria are inconclusive for therapeutic decision-making. If indicated, chemotherapy can be used either after surgery (adjuvant) or before surgery (neoadjuvant). Both approaches lead to comparable long-term survival. The neoadjuvant setting offers the additional opportunity for elaborate translational studies to develop and validate predictive biomarkers and to discover mechanisms of resistance to therapy. If possible, chemotherapy regimens should include both anthracyclines and taxanes. Docetaxel should be used every 3 weeks; better tolerability with equivalent efficacy favors the concurrent over the sequential approach. Paclitaxel, on the other hand, should be administered sequentially, either weekly or every 2 weeks. Especially, intense dose-dense sequential chemotherapy with granulocyte colony-stimulating factor support is very effective in high-risk breast cancer patients. In order to decrease toxicities, anthracycline-free regimens or a shortening of the duration of adjuvant chemotherapy are potential options that should be further explored.
Breast cancer; Prognosis; Chemotherapy
Sorafenib was tested for neoadjuvant treatment with an anthracycline/taxane-based chemotherapy in the open-label, multicentre, single-arm phase II study, ‘SOFIA’.
Patients and Methods
Inclusion criteria were: HER2 negative, cT3, cT4 or cT2 cN+, M0 primary breast cancer. Patients received 4 × epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 (EC) intravenously (i.v.) in 3-weekly cycles followed or preceded by 12 weeks of paclitaxel (Pw) 80 mg/m2. In cohort 1, sorafenib started at 800 mg daily with chemotherapy. An initial daily sorafenib dose of 200 mg was escalated, based on individual toxicities, every 3 weeks in cohort 2 (starting with EC) and every 2 weeks in cohort 3 (starting with Pw). The primary objective was to identify the most feasible regimen; secondary objectives were safety, pathological complete response (pCR) at surgery and pharmacokinetics.
Of the 36 recruited patients, 7/12 patients completed the study in cohort 1 and 24/24 patients in cohorts 2 and 3. The median cumulative sorafenib dose per patient was 37%, 65% and 46% in cohorts 1, 2 and 3, respectively. The main grade 3–4 toxicities were neutropenia and hand-foot syndrome. The pCR (ypT0/is) rate was 27.7%. No pharmacokinetic interaction was observed between sorafenib and epirubicin.
Sorafenib EC-Pw is feasible if the starting dose is 200 mg, escalated every 3 weeks based on the patients’ individual toxicities.
Breast cancer; Sorafenib; Pharmacokinetics; Anthracycline; Taxane
In 2014, modern strategies of targeted therapies in the adjuvant setting are mainly focused on anti-human epidermal growth factor receptor 2 (HER2) blockade. For the 15% of HER2-enriched tumors, 1 year of treatment with the monoclonal antibody trastuzumab is the standard of care. All patients, regardless of tumor size, nodal status, or age, profit from therapy with risk reduction rates for recurrence of up to 50%. As a consequence, the current guidelines recommend the use of trastuzumab in these patients if additional risk factors lead to the consideration of adjuvant chemotherapy. The concurrent use with taxane-based chemotherapy is preferred. The concept of dual HER2 blockade – already approved in the metastatic setting – shows also significantly improved efficacy in neoadjuvant trials. Dual blockade with trastuzumab and pertuzumab is approved by the Food and Drug Administration (FDA) for neoadjuvant treatment of HER2-overexpressing tumors. However, until approved in Europe, this treatment approach remains off-label for early breast cancer and study participation is highly recommended. Bisphosphonates (BPs) and denosumab are approved in breast cancer as standard therapy for the treatment of bone metastases. In the adjuvant setting, BPs and denosumab can be given to prevent tumor therapy-induced bone loss. The antineoplastic effect of BPs in the adjuvant setting and its role in the prevention of metastatic disease are still under discussion.
Early breast cancer; Targeted therapy; HER2; Osteo-oncology
Many types of cancer are associated with polymorphisms of the renin-angiotensin system. Our aim was to assess possible association between single-nucleotide polymorphisms (SNPs) of the angiotensin II receptor types 1 (A168G), and 2 (T1247G and A5235G) with breast cancer.
Patients and Methods
242 participating subjects were genotyped and allocated to case or control groups.
Genotype distribution (in %) was: for AGTR1 (A168G): AA, AG, GG = 61, 30, 09 for cases, and 69, 25, 06 for controls (p = 0.55); for AGTR2 (T1247G): TT, TG, GG = 84, 12, 04 for cases, and 81, 17, 02 for controls (p = 0.45); for AGTR2 (A5235G): AA, AG, GG = 32, 67, 01 for cases, and 53, 28, 19 for controls (p < 0.0001). Women carrying genotypes AA/AG in the intronic region of angiotensin II type 2 receptor had an 11-fold higher risk of breast cancer than GG carriers.
Many types of cancer have been associated with polymorphisms of the renin-angiotensin system. For SNP A5235G, the GG genotype seems to be protective against breast cancer. The other 2 SNPs showed no association. However, SNPs T1247G and A5235G were associated with at least 1 clinical variable, with G being a predictor of better outcome. The use of SNPs A5235G and T1247G (the latter to a lesser degree) as genetic markers should be considered.
Angiotensin II type 1 receptor; Angiotensin II type 2 receptor; Breast neoplasm; Genetic polymorphisms; Genotyping
Melatonin is an endocrine hormone secreted by the pineal gland during night hours that provides several biological functions in the circadian rhythm of humans. Due to anti-estrogenic properties, melatonin is considered to exhibit a protective role against the development of breast cancer (BC). Moreover, disruption of melatonin production through environmental influences, such as night work, is assumed to be a risk factor for BC.
Materials and Methods
We reviewed recent findings concerning biological effects of melatonin on BC and conducted a meta-analysis to evaluate the association between melatonin and BC incidence. In random and fixed effects statistical models, concentrations (tertiles, quartiles) of the primary urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), were tested for the assumption that women with the highest values would exhibit a lower risk of BC.
Statistical analysis of data from 5 prospective case-control studies indicates an inverse association between BC risk and the highest levels of urinary aMT6s. This effect seems to be influenced by lag intervals between aMT6s collection and the occurrence of BC, timing and methods of urine sampling, as well as genetic and environmental factors.
On the basis of the results of our meta-analysis, melatonin is likely to affect BC occurrence in women. However, methodological dissonances may require further studies.
Melatonin; aMT6s; Urinary excretion; Meta-analysis; Breast cancer
Guidelines; Locoregional relapse; Metastatic breast cancer; Targeted therapy
In Turkey, the gene expression profile test is not standard, so adjuvant treatment is planned according to clinicopathological factors. Therefore, we retrospectively analyzed important parameters that affect the decision on adjuvant chemotherapy, and also factors related to survival in stage IA breast cancer patients in Turkey.
We retrospectively evaluated 347 stage IA patients. The relationship between the clinicopathological parameters and adjuvant chemotherapy was analyzed.
The median age and follow-up time were 52 years (range: 25–86) and 22.6 months (range: 1–113), respectively. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 87.9% and 98.7%, respectively, but the median DFS was not reached. Age, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, and the presence of triple-negative breast tumor (TNBC) were related to DFS, and lymphovascular invasion (LVI), perineural invasion (PNI), HER2 status, the presence of TNBC, and recurrence were related to OS (p > 0.05). Furthermore, age, menopausal status, multicentricity, grade, tumor size, necrosis, ER, the presence of TNBC, and HER2 were found to be related to adjuvant therapy decision (p > 0.05). All these parameters, in addition to LVI and PNI, were independent factors for chemotherapy by logistic regression analysis.
In decisions about adjuvant therapy in stage IA breast cancer patients, clinicopathological factors should be kept in mind.
Breast cancer; Stage IA; Adjuvant therapy; Chemotherapy
Brain metastases (BM) are an increasing challenge in modern oncology, as treatment options especially after exhaustion of local treatment approaches are very limited.
Patient and Methods
A long-term surviving patient with brain-only metastatic breast cancer, who presented at our department with massive corticosteroid-refractory brain edema with serious neurological symptoms after exhaustion of all local therapy options, was started on bevacizumab.
Initiation of bevacizumab monotherapy led to rapid decrease of contrast-enhancing lesions and alleviation of brain edema, and allowed tapering and termination of corticosteroid administration. Neurological and neurocognitive function was restored and marked improvement in quality of life was observed.
Our case highlights that bevacizumab may represent a feasible and effective salvage treatment option in selected patients with BM.
Breast cancer; Brain metastases; Neurocognitive functioning; Bevacizumab; Symptom control; Brain edema
Idiopathic granulomatous mastitis (IGM) is an uncommon chronic inflammatory disease of the breast with uncertain optimal treatment regimen. In this study, our purpose was to report our clinical experience with 74 IGM patients who were treated wide local excision with or without steroid therapy.
Patients and Method
74 cases diagnosed histologically as IGM were identified from surgical and pathological records between January 1995 and January 2012. Group 1 (surgery-only group) comprised 53 patients, and the 21 patients in group 2 were treated with corticosteroids prior to surgical treatment (steroid-and-surgery group).
Follow-up data were complete for 67 (91.7%) of the 73 patients. Recurrence developed in 4 (7.5%) patients in the surgery-only group, while there was no recurrence in the steroid-and-surgery group; the difference was not statistically significant (p = 0.19).
Systemic steroid therapy with surgical resection is the recommended first-line treatment strategy for IGM.
Idiopathic granulomatous mastitis; Wide excision; Corticosteroid therapy
The usefulness of distress screening in cancer inpatient settings has rarely been investigated. This study evaluated a brief distress screening of inpatients in a breast cancer centre and a gynaecological cancer centre.
Patients and Methods
Hospitalised patients with breast or gynaecological cancers were screened with the Distress Thermometer. Patients who scored above the cut-off, were referred by the medical staff, or self-referred were offered bedside psycho-oncological counselling.
Of 125 patients, 68 (54.4%) received an offer of counselling, and 62 patients (49.6%) accepted. Most of the counselling was induced by distress screening. Only 4 (3.2%) patients self-referred to the counselling service. Of the counselled patients, 65.8% stated that they had substantially benefited from psycho-oncological support; only 5.6% of the non-counselled patients indicated that they might have benefited from psycho-oncological support.
Almost all patients who will accept and benefit from psycho-oncological counselling can be identified if distress screening is used in conjunction with referrals by physicians and nurses. Distress screening is a worthwhile component in a framework of psycho-oncological support in a cancer inpatient setting. It paves the way to counselling for cancer inpatients who need it and are willing to accept it but hesitate to self-refer to psycho-oncological services.
Distress screening; Psychosocial distress; Distress Thermometer; Psycho-Oncology; Counselling
Intraoperative radiotherapy during breast-conserving surgery is being studied as an alternative to 6 weeks of external beam radiotherapy (EBRT) for low-risk women; it can be delivered using electrons (intraoperative electron radiotherapy, IOERT) or 50-kV X-rays.
Materials and Methods
We analyzed both single institutional and randomized studies involving single-fraction IOERT treatments. Rates for ipsilateral breast tumor recurrences, disease-specific survival, and overall survival were obtained.
IOERT had true 5-year recurrence rates of > 1.5% for ASTRO (American Society for Radiation Oncology) and ESTRO (European Society for Therapeutic Radiology and Oncology) suitable women, or for low-risk women as defined by the ELIOT trial. Women with ductal carcinoma in situ eligible for breast-conserving therapy, older women that currently receive no EBRT, and younger women with favorable biology are additional potential candidates.
ASTRO suitable and ESTRO good women for accelerated partial breast irradiation are low-risk groups. Higher-risk women with favorable biology might also be suitable candidates for IOERT, providing the tumor biology can be determined prior to surgery. For intraoperative radiotherapy using 50-kV X-rays, follow-up was too short to assess the effectiveness of the treatment.
Breast cancer; Radiotherapy; Academic Review
During the last decade, besides the well-established clinical-pathological predictors for the risk of late recurrence in breast cancer, such as estrogen receptor status, and T and N stage, a variety of multigene assays have been shown to improve prognostication and prediction in this setting. Several clinical trials have evaluated the role of extended endocrine therapy with tamoxifen (ATLAS) or aromatase inhibitors (MA.17, NSABP-B33 and ABCSG 6a), and other randomized studies are still ongoing. However, among this patient population, it is still not clear who could benefit from extended therapy and what the optimal treatment duration should be. New multigene assays such as EndoPredict, PAM50 ROR-score, HOXB13/IL17BR ratio and Breast Cancer Index provide significant and relevant prognostic information concerning the likelihood of recurrence beyond 5 years after surgery. The identified low-risk subgroups not only show a very favorable prognosis, they also seem to have only little benefit from extended aromatase inhibitor therapy. Many of these reverse transcriptase/polymerase chain reaction-based techniques have been validated in archived tumor material from large phase III trials, and will soon be available to routine pathology laboratories as an aid in clinical decision-making for patients.
Breast neoplasms; Late metastasis; Endocrine therapy; Prediction
Core needle biopsy (CNB) is widely accepted for preoperative diagnosis of breast cancer and sometimes can be the only way of providing a suitable specimen for prognostic and predictive marker studies prior to neoadjuvant treatment. The purpose of this study was to evaluate the accuracy of CNB by comparing histological tumor type and grade as well as estrogen receptor (ER), progesterone receptor (PR), p53, and HER2/ neu status by immunohistochemistry in CNB and excisional surgical specimens.
Patients and Methods
During a 2.5-year study period, we identified 30 patients with breast cancer, who underwent CNB and definitive surgery. To evaluate the accuracy of CNB, tumor grade, ER, PR, HER2, and p53 status were immunohistochemically determined in both the CNB and the surgical specimens, and concordance of results between the 2 specimens was assessed.
The concordance rate was 100% for histological type, 66.6% for histological grade, and 96.7, 90, 76.7 and 93.3% for ER, PR, p53 and HER2/neu, respectively.
Our study showed that CNB has an excellent accuracy for tumor type, ER, and HER2/ neu; however, it should be used cautiously for tumor grade, PR, and p53 status. Thus, excisional biopsy is recommended for the determination of these factors.
Prognostic factors; Breast cancer; Core needle biopsy
Local treatment of the axilla in clinically node-negative, early-stage breast cancer patients has been hotly debated after the release of the American College of Surgeons Oncology Group (ACOSOG) Z0011 findings. However, this review does not focus on the ‘Z0011-eligible’ patients alone, because this subgroup represents a minority of our patients undergoing breast-conserving surgery (BCS) and sentinel lymph node biopsy (SLNB). The following topics are discussed: axillary diagnostics, timing of axillary procedures in the neoadjuvant setting, long-term follow-up of SLNB trials, omission of axillary surgery in randomized trials, management of the involved axilla with low tumor volume, positive sentinel lymph nodes and BCS, involved sentinel lymph nodes and mastectomy, and axillary radiotherapy. Finally, the current innovative study concepts (i.e. Sentinel Node versus Observation after Axillary Ultrasound (SOUND) and Intergroup Sentinel Mamma (INSEMA)) including patients with axillary observation alone in clinically node-negative women are presented.
Breast cancer; Axilla; Surgery; Radiotherapy; INSEMA
The current surgical debate has led to a reduction in the extent of surgery performed and thereby to a reduced occurrence of surgical trauma and, over the recent years, reduced seroma formation. This reduction in surgical procedures calls the need for a drain into question.
Using Google Scholar and the National Library of Medicine (PubMed), a literature review was performed on systematic reviews and meta-analyses regarding breast cancer surgery ± axillary dissection. Additionally, randomized trials for the time period after the last systematic review were included and evaluated according to the Jadad score.
The search returned 5 systematic reviews, in which a total of 1,075 patients were included (537 cases and 538 controls). Since the last review, no prospective randomized trial meeting the inclusion criteria has been published. The current reviews conclude that insertion of a drain is associated with a longer hospital stay and reduced seroma formation. The data regarding wound infection and drain insertion is inconclusive. The omission of a drain is associated with early discharge, reduced postsurgical pain, and early mobilization, but also with an increase in outpatient seroma aspirations.
The omission of a drain is possible in early breast cancer surgery (wide local excision and sentinel node biopsy) with adequate surgical techniques and instruments.
Breast cancer; Surgery; Drain; Wound; Seroma; Sentinel; Breast conserving
Oral mucositis (OM) is a clinically important and frequent adverse event (AE) associated with cancer treatment with conventional chemotherapy as well as new targeted agents. Incidence and severity of OM vary from treatment to treatment and from patient to patient. The pathogenesis of chemotherapy-induced OM can be divided into 5 phases. OM induced by targeted therapies differs among other things in appearance, course, concomitant AEs and toxicity, and thus could be perceived as an entity distinct from chemotherapy-induced OM with an innate pathogenic mechanism. OM has a severe impact on a patient's quality of life (QoL) by causing complications such as pain and discomfort. Even more important are associated restrictions in nutrition and hydration. Thus, the efficacy of cancer therapy might be impaired due to the necessity of dose delays and dose reductions. Numerous preventive and therapeutic approaches have been evaluated, but currently no single agent has changed the standard of care in preventing and treating OM. Thus, the current management has evolved from clinical experience rather than clinical evidence. This article will review the AE ‘OM’ induced by breast cancer treatment with chemotherapy and targeted agents in order to provide practical guidance for management and prevention.
Oral mucositis; Disease management; Breast cancer; Chemotherapy; Molecular targeted therapy
Trastuzumab improves the survival of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). The incidence and long-term impact of trastuzumab-related cardiotoxicity in the community setting is of great clinical importance.
Material and Methods
Patients with HER2-positive BC treated with (neo)adjuvant trastuzumab were retrospectively evaluated. Cardiotoxicity was defined as cardiac death or absolute decrease in left ventricular ejection fraction of at least 10% to a value less than 50%, or symptomatic heart failure.
We evaluated 237 patients: median age 53 years (range 27–83 years). 40.5% of these patients had received neoadjuvant and 59.5% adjuvant chemotherapy. The majority (83.9%) were treated with an anthracycline-based regimen. Median exposure to trastuzumab was 8 months (range 2–12 months). Cardiotoxicity was diagnosed in 20.2%, but symptoms only occurred in 3.8%. 41.6% recovered cardiac function. None of the risk factors were associated with cardiotoxicity.
The incidence of trastuzumab-related cardiotoxicity found in this study was slightly higher than those reported in randomized clinical trials. Nevertheless, most patients were asymptomatic. We describe the cardiac outcomes of a non-selected population, which possibly reflects those found in the ‘real world’. The risks versus benefits of trastuzumab use remain in favor of treatment, but cardiotoxicity should be monitored.
Adjuvant therapy; Breast cancer; Cardiotoxicity; Trastuzumab
Advances in our understanding of the pathophysiology of chemotherapy-induced nausea and vomiting (CINV), the identification of patient risk factors, and the development of new antiemetics have led to significant improvements in CINV prevention. With the correct use of antiemetic drugs, CINV can be prevented in the majority of patients. Extensive clinical data have been considered in the development of antiemetic treatment recommendations by reliable institutions such as the Multinational Association of Supportive Care in Cancer, the European Society of Medical Oncology and the American Society for Clinical Oncology. These guidelines are intended to enable physicians to incorporate the latest clinical research into their daily practice, considering CINV prevention as part of an optimal patient-centered approach to cancer management. Yet despite the availability of these guidelines, there is emerging evidence that implementation of treatment recommendations is suboptimal. Recently, guideline committees gave special consideration to patient-related risk factors (young, females) contributing to the emetogenic potential for patients receiving anthracycline and cyclophosphamide-based chemotherapy. As women with breast cancer represent a particularly challenging population regarding emesis control, it is especially important that treatment recommendations are followed. This review focuses on the content of the current antiemetic guidelines, addressing the importance of how these are intended to be implemented in routine clinical practice.
Chemotherapy-induced nausea and vomiting; Antiemetic guidelines; 5-HT3 receptor antagonists; Neurokinin receptor antagonist
Metastasized male breast cancer (MMBC) is a rare disease. Given its low incidence, data regarding tumor biology, current treatment options, and survival rates are scarce.
Patients and Methods
A chart review was performed of MMBC patients consecutively registered in regional cancer registries in Germany between 1995 and 2011. Tumor characteristics, treatment, and survival rates were documented and statistically evaluated.
41 men with MMBC represented 25.6% of a total of 160 patients with MBC. 16 (39%) patients showed primary metastases, and 25 (61%) had recurrent metastases. Median survival from occurrence of metastasis was 32 months. Median overall survival (OS) was 68 months. 68.3% (n = 28) of the cohort received systemic therapy favoring endocrine therapy (n = 25, 61.9%). Prolonged metastatic OS (p = 0.02) was observed in patients having had a systemic treatment. Metastatic patients having received endocrine treatment showed significantly prolonged survival rates. Furthermore, patients receiving palliative chemotherapy had a significant survival benefit compared to those in whom chemotherapy was omitted.
Our results suggest that systemic treatment in the form of both palliative chemotherapy and endocrine therapy improves outcome of R. Foerster and L. Schroeder contributed equally to this article and are listed in alphabetical order. MMBC. Therefore, it seems reasonable that treatment of MMBC should be based on the guidelines for female breast cancer.
Male breast cancer; Metastasis; Prognosis