Cisplatin–gemcitabine therapy in metastatic breast cancer: Improved outcome in triple negative breast cancer patients compared to non-triple negative patients

Triple negative or basal-like breast cancers lack expression of estrogen, progesterone and HER2neu receptors. There are no specific treatment guidelines for this group of patients, however, it has been postulated that their phenotypic and molecular similarity to BRCA-1 related cancers would confer sensitivity to certain cytotoxic agents like cisplatin (CDDP). The aim of the study was to retrospectively examine the clinical outcome at our institution of patients with metastatic breast cancer treated with CDDP and gemcitabine combination chemotherapy who had triple negative breast cancer compared to non-triple negative breast cancer. Thirty-six patients with metastatic breast cancer were treated with CDDP and gemcitabine combination chemotherapy, 17 of whom were triple negative (47%) and 19 were non-triple negative (53%). The median progression free survival for triple negative and non-triple negative metastatic breast cancer patients were 5.3 months and 1.7 months respectively (p = 0.058). By multivariate Cox proportional hazard model after adjusting for age, race and menopausal status the risk of progression was reduced by 47% for triple negative compared to non-triple negative metastatic breast cancer patients (HR = 0.53, p = 0.071).ConclusionsOur results suggest an improved outcome for metastatic triple negative breast cancer patients compared to non-triple negative breast cancer patients when treated with cisplatin and gemcitabine combination chemotherapy.     

Morphometry of isolated tumor cells in breast cancer sentinel lymph nodes: metastases or displacement?

Iatrogenic displacement and mechanical transport of epithelial cells to the sentinel node (SN) has been suggested to result in false-positive findings in breast cancer patients, but little biologic evidence has yet been presented for this hypothesis. As malignant nuclei are larger than benign ones, nuclear morphometry of SN isolated tumor cells (ITC) could provide relevant information with regard to the malignant origin-or-not of epithelial cells in the SN. In patients with primary invasive breast cancer and SN ITC with (N=16) or without (N=45) non-SN involvement, nuclear morphometry was performed on the primary tumor as well as on the ITC in the SN. Nuclear size in the primary tumor was compared with that in the corresponding ITC. Patients with SN micrometastases (N=30) and SN macrometastases (N=30) served as controls. Nuclear size of ITC was significantly smaller compared with nuclear size of the corresponding primary tumor (P<0.0001). In contrast, there were no differences in nuclear size between SN micrometastases and macrometastases on the one hand and their corresponding primary tumors on the other. In addition, a subgroup of cases (10/61, 16%) with benign morphometric features of SN ITC nuclei (small and isomorph) could be discerned that had no non-SN metastases. In conclusion, nuclei of SN ITC are significantly smaller compared with the corresponding primary tumor and are often not associated with non-SN involvement. This supports the hypothesis that some of these deposits could represent benign epithelium or degenerated malignant cells lacking outgrowth potential.     

Can axillary lymph node dissection be omitted in patients with breast cancer and positive sentinel nodes?

Sentinel lymph node biopsy has evolved as the surgical procedure of choice for women with clinically negative axillae, as part of an effort to move toward the less invasive surgical management of breast cancer. Axillary lymph node dissection remains the standard of care for patients with a positive axillary node and was previously performed on all patients with breast cancer prior to the implementation of the sentinel lymph node biopsy. There is, however, controversy regarding whether or not all patients with a positive sentinel lymph node need to undergo completion axillary dissection for either prognostic or therapeutic purposes. This article reviews the literature related to this controversial and evolving topic.     

Effects of guideline adherence in primary breast cancer–A 5-year multi-center cohort study of 3976 patients

BackgroundThe aim of that study was to analyze the impact of German-S3-breast cancer guideline adherence on clinical outcomes.MethodsA retrospective study analyzed 3976 patients first diagnosed with primary breast cancer according to an S3-guideline-based model that classified patients retrospectively into groups receiving “guideline-adherent and “guideline non-adherent” therapy.ResultsThere was a significant association between treatment adherence and prolonged recurrence free and overall survival (p = 0.0001). The greater the number of violations in guideline adherence, the lower was overall survival (p = 0.0001). Advanced age at initial diagnosis was additionally associated with a reduction in guideline adherence. The percentage of guideline adherence for the therapeutic modalities BCT, mastectomy, axillary dissection and hormone therapy was greater than 80%. For chemotherapy, the percent of guideline adherence totaled 71.4%.ConclusionTherapies dispensed in adherence with guidelines may improve recurrence-free survival and overall survival in patients with breast cancer.     

Comorbidity‐dependent adherence to guidelines and survival in breast cancer—Is there a role for guideline adherence in comorbid breast cancer patients? A retrospective cohort study with 2137 patients

In the treatment of breast cancer, decisions on adjuvant treatment reflect individual patient characteristics like age and comorbidity. This study assessed the association between adherence to guidelines for adjuvant treatment and survival while taking into account age at diagnosis and comorbidities. We collected the Charlson comorbidity index at baseline for 2179 women treated for primary breast cancer from 1992 to 2008 who participated in a German retrospective multicenter cohort study. We assessed subsequent adjuvant therapy guideline adherence and survival in relation to baseline comorbidities. Guidelines for adjuvant chemotherapy and radiotherapy were more often violated in patients with higher Charlson score. Patients with higher Charlson scores received chemotherapy and radiotherapy less often and had higher rates of mastectomy. Irrespective of comorbidity (Charlson score 0, 1‐2, ≥3), patients with 100% guideline‐adherent adjuvant treatment showed better overall and disease‐free survival (DFS) compared to patients with guideline violations (GVs). Controlling for age, comorbidity and tumor characteristics, the hazard ratio for at least one GV was 1.65 (95% confidence interval [CI]: 1.33‐2.07) for overall survival and 1.84 (95% CI: 1.53‐2.22) for DFS. Guideline‐adherent treatment was significantly less frequent in comorbid patients, although guideline adherence was strongly associated with improved survival, irrespective of severity, and number of comorbid diseases.     

PD-1, PD-L1 and CTLA-4 in pregnancy-related – and in early-onset breast cancer: A comparative study

PurposeWe aimed to compare the immunohistochemical expression of PD-1, PD-L1 and CTLA-4 of pregnancy-related breast cancer (PRBC) and early onset non-PRBC (YWBC), and their prognosis prediction potential was correlated to that of conventional clinicopathological factors.MethodsTwenty-one PRBC cases were paired with 21 YWBC in this matched case-control study. Immune-checkpoint markers (ICM) were evaluated with immunohistochemistry (IHC) on whole slides using the following antibodies: PD-1 (NAT-105), PD-L1 (28-8) and CTLA-4 (F-8). IHC score was defined as the percentage of positive cells, assessed separately among tumor cells, intratumoral lymphocytes and peritumoral lymphocytes.ResultsThe optimal threshold of PD-L1 expression of tumor cells occurred at 10% for overall survival (OS, AUC = 0.847, p = 0.009), and at 1% for disease-free survival (DFS, AUC = 0.795, p = 0.010). For PD-L1 expression on intratumoral lymphocytes, the optimal cut-off was 1% (AUC = 0.763, p = 0.048). Considering PD-1, PD-L1 and CTLA-4 expression, no significant difference occurred between PRBC and YWBC (p > 0.05 for all comparisons). PD-1, PD-L1 expressed on peritumoral lymphocytes and CTLA-4 failed, but PD-L1 expressed on tumor cells and on intratumoral lymphocytes was suitable to distinguish patient cohorts with different OS and DFS (p ≤ 0.011 for all comparisons). Higher PD-L1 expression was associated with poor prognosis. PD-L1 expressed on tumor cells represented an independent association with OS (p = 0.023) and DFS (p = 0.032).ConclusionsOur results suggest that PRBC and YWBC do not differ in the expression of PD-1, PD-L1 and CTLA-4. However, our findings emphasize the relevance of PD-L1 expression in early-onset breast cancer, as an independent negative predictor of prognosis.     

Clinical outcomes of cyclin-dependent kinase 4–6 (CDK 4–6) inhibitors in patients with male breast cancer: A multicenter study

BackgroundSince breast cancer is less common in men than in women, data on the use of new therapeutic agents, including cyclin-dependent kinase 4–6 (CDK 4–6) inhibitors, are limited in patients with metastatic hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) male breast cancer. Therefore; we aimed to investigate the treatment responses of metastatic HR+, HER2-male breast cancer patients treated with CDK 4–6 inhibitors in a multicenter real-life cohort.MethodsMale patients with a diagnosis of HR+ and HER2-metastatic breast cancer, treated with any CDK 4–6 inhibitor, were included in the study. Demographic and clinical characteristics of the patients were recorded. We aimed to determine progression-free survival (PFS) time, response rates and drug related side effects.ResultsA total 25 patients from 14 institutions were recruited. The mean age at diagnosis was 57 years. Median follow-up was 19.53 (95% CI: 14.04–25.02) months. The overall response rate was 60%. While the median PFS was 20.6 months in the whole cohort, it wasn't reached in those using CDK 4–6 inhibitors in first line and 10 months in the subsequent lines (p:0.009). No new adverse events were encountered.ConclusionIn our study, we found that CDK 4–6 inhibitors are effective and safe options in men with HR+ and HER2-metastatic breast cancer as in women. Our results support the use of CDK 4–6 inhibitor-based combinations in the first-line treatment of HR+ and HER2-metastatic male breast cancer.     

Axillary reverse mapping in N0 patients requiring sentinel lymph node biopsy – A systematic review of the literature and necessity of a randomised study

ObjectivesAxillary reverse mapping (ARM) is a technique to map and preserve arm lymphatics which may be damaged during surgery, resulting in lymphoedema.This work systematically reviews the incidence of lymphoedema following sentinel lymph node biopsy (SLNB) + ARM, compared to SLNB alone, for clinically node negative disease, as well as recurrence rate, other morbidity and the feasibility and difficulties of ARM.Materials and MethodsThe following databases were searched: PubMed, Embase, Cochrane Library. Abstracts submitted to recognised societies dedicated to research in oncology were included. Studies were eligible if performed within the last 10 years; ARM was used in any form; ARM performed during SLNB ± axillary lymph node dissection (ALND). Studies were analysed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsNo studies were found meeting the initial inclusion criteria. Therefore, studies reporting use of SLNB + ARM (i.e. no comparison to SLNB) were reviewed. A second search was performed to identify studies reporting outcome following SLNB alone. Twelve studies reported data on patients undergoing SLNB + ARM and 23 studies on patients undergoing SLNB. Incidence of lymphoedema following SLNB + ARM was quoted between 0-4% and 0–63.4% following SLNB. Few studies commented on recurrence rate. Studies included were of mainly low level of evidence.ConclusionEvidence is beginning to emerge for the use of ARM in order to reduce lymphoedema following axillary surgery. However, data regarding oncological safety of ARM is not clear and randomised controlled trials, with adequate follow-up, need to be performed to determine this.     

Lumbar instrumented posterolateral fusion in spondylolisthetic and failed back patients: a long-term follow-up study spanning 11–13?years

Introduction and materials

We examined lumbar transpedicular instrumented posterolateral fusion patients operated on between 1992 and 1997 presenting: degenerative spondylolisthesis with spinal stenosis; adult isthmic spondylolisthesis; failed back syndrome after one to five discectomies; and failed back syndrome after one to three laminectomy operations (Groups 1–4, respectively).

Methods

They were examined by an independent orthopedic surgeon, completed the Oswestry Disability Index (ODI) and visual analog scale (VAS) questionnaires and their outcome was evaluated.

Results

The overall patient satisfaction at follow-up (mean 11.7 years) was 82.1 %. The reoperation rate was 15.1 % (7.5 % due to adjacent segment disease).

Conclusion

Group 1 showed the greatest improvements in ODI and VAS values, Group 2 the lowest and Group 3 the highest preoperative values, and Group 4 the second highest improvements. Patient satisfaction scores were 90.3, 69.7, 63.6 and 80.0 %, respectively, and unplanned reoperation rates were 6.5, 9.1, 31.8 and 20.0 %. Thus, long-term outcomes of lumbar instrumented posterolateral fusion (rarely previously studied) were satisfactory for >80 % of patients, but varied among groups.     

Impact of schizophrenia and related disorders on mortality from breast cancer: A population-based cohort study in Denmark, 1995–2011

ObjectivesTo investigate overall and breast cancer-specific mortality in early-stage breast cancer patients with and without schizophrenia or related disorders.MethodsWe used Danish national registers to identify all women with no prior history of cancer or organic mental disorders, who were diagnosed with early-stage breast cancer 1995–2011. Logistic regression models were used to calculate the odds ratios (ORs) for not being allocated to guideline treatment. Cox regression models were used to compute hazard ratios (HRs) for overall and breast cancer-specific deaths among women allocated or not allocated to guideline treatment.ResultsWe identified 56,152 women with early-stage breast cancer diagnosed in 1995–2011, of whom 499 women also had been diagnosed with schizophrenia or related disorders. The likelihood of women with schizophrenia or related disorders for not being allocated to guideline treatment was increased (adjusted OR, 1.50; 95% confidence interval (CI), 1.15–1.94). The adjusted HR for all-cause mortality was 1.55; 95% CI, 1.32–1.82 and 1.12 (95% CI, 0.98–1.50) for breast cancer-specific mortality; women allocated to guideline treatment had an adjusted HR for breast cancer-specific death of 1.42 (95% CI, 1.11–1.82). The adjusted HR for death due to unnatural causes was 3.67 (95% CI, 1.80–7.35).ConclusionThe survival of women with schizophrenia or related disorders after breast cancer is significantly worse than that of women without these disorders. These patients are less likely to be allocated to guideline treatment, and, among those who are, mortality from both breast cancer and other causes is increased.     

Is extracapsular nodal extension in sentinel nodes a predictor for nonsentinel metastasis and is there an impact on survival parameters?—A retrospective single center cohort study with 324 patients

The Z0011 trial has fundamentally changed axillary management in breast cancer patients. However, some important questions remain, like the role of extracapsular nodal extension (ENE) in positive sentinel nodes and the need for further axillary treatment. In this retrospective cohort study, we reviewed and analyzed data from 342 clinically node negative (cN0) breast cancer patients with a positive sentinel node and subsequent axillary lymph node dissection (ALND) from the BRENDA data base. The 104 (30.4%) ENE positive patients had a significantly higher proportion of ≥3 positive axillary lymph nodes (65.0%) compared to ENE negative patients with a positive sentinel node (21.4%). Likewise, ENE positive patients had significantly more often lymph node metastasis size >2 mm (96.2%) than ENE negative patients (72.7%). T1 status was observed significantly more often in ENE negative patients (53.2%) than in ENE positive patients (24.0%). While ENE was linked to worse overall survival in univariate analysis, this effect disappeared when adjusting for nodal status, age, and comorbidities in multivariate analysis. ENE of the sentinel node is an important predictor for nonsentinel lymph node involvement. We suggest that ENE influences survival only via a higher number of positive nodes – one of the most predictive parameters for survival outcome in breast cancer.     

Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case–control study of 87 cases

Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival.We conducted a retrospective unicenter case–control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis.Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0–T2 and T3–T4 PABC patients have the same poor prognosis as control BC patients with T3–T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients.Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step.