Accompanying DCIS in breast cancer patients with invasive ductal carcinoma is predictive of improved local recurrence-free survival

BackgroundDuctal carcinoma in situ (DCIS) often accompanies invasive ductal carcinoma (IDC). The presence of co-existing DCIS is postulated to present as a less aggressive phenotype than IDC alone.Patients and methodsPatients diagnosed with hormone receptor-positive breast cancer receiving mastectomy were evaluated. Only patients without adjuvant radio- and chemotherapy were included to decrease treatment bias on local recurrence (LR).ResultsOf 2239 breast cancer patients, 198 fulfilled the inclusion criteria. The overall LR rate was 11.6%. Tumor stage (p = 0.002), nodal status (pN2 vs. pN0, p = 0.023) and pure IDC compared with IDC-DCIS (p = 0.029) were multivariate independent factors for increased LR risk. Patients with IDC-DCIS were significantly younger (p < 0.001), had smaller tumors (p = 0.001), less lymph node involvement (p = 0.012). The LR rate was significantly increased in patients with pure IDC (p = 0.012). The time to distant metastases was decreased in patients with pure IDC compared with that observed in patients with IDC-DCIS (log rank = 0.030).ConclusionInvasive ductal carcinoma accompanied by DCIS is associated with lower LR. The prognostic value of co-existing DCIS in the adjuvant decision-making process may be considered a new independent prognostic marker. This finding needs further studies to evaluate its usefulness in premenopausal women.     

Clinical development of CDK4/6 inhibitor for breast cancer

Endocrine therapy is the mainstay of treatment for patients with estrogen receptor positive (ER+)/HER2-negative (HER2?) metastatic breast cancer (MBC). Many clinicians consider the sequential endocrine therapy is gold standard strategy because of better outcome and the maintenance of a better quality of life (QOL) for MBC patients. However, clinical practice shall be changed according to development of CDK4/6 inhibitor in current. CDK4/6 is key kinase which promote the cell cycle, and especially the expression of cyclin D1 and the activation of CDK4/6 to drive breast cancer proliferation. Currently positive data of several clinical trials using three CDK4/6 inhibitors (palbocilcib, ribociclib, abemaciclib) were published and primary endpoint were met in all phase III studies. Therefore, practice change of endocrine therapy has been achieved in ER positive MBC. This review will present clinical trial data, including both the efficacy and safety of CDK4/6 inhibitors for MBC, and describe the designs of the mainly ongoing clinical trials examining CDK4/6 inhibitors for the treatment of MBC and EBC.     

Circ_0008039 supports breast cancer cell proliferation,migration, invasion,and glycolysis by regulating the miR‐140‐3p/SKA2 axis

Circular RNAs (circRNAs) have been shown to modulate gene expression and participate in the development of multiple malignancies. The purpose of this study was to investigate the role of circ_0008039 in breast cancer (BC). The expression of circ_0008039, miR‐140‐3p, and spindle and kinetochore‐associated protein 2 (SKA2) was detected by qRT‐PCR. Cell viability, colony formation, migration, and invasion were evaluated using methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay, colony formation assay, and transwell assay, respectively. Glucose consumption and lactate production were measured using commercial kits. Protein levels of hexokinase II (HK2) and SKA2 were determined by western blot. The interaction between miR‐140‐3p and circ_0008039 or SKA2 was verified by dual‐luciferase reporter assay. Finally, a mouse xenograft model was established to investigate the roles of circ_0008039 in BC in vivo. We found that circ_0008039 and SKA2 were upregulated in BC tissues and cells, while miR‐140‐3p was downregulated. Knockdown of circ_0008039 suppressed BC cell proliferation, migration, invasion, and glycolysis. Moreover, miR‐140‐3p could bind to circ_0008039 and its inhibition reversed the inhibitory effect of circ_0008039 interference on proliferation, migration, invasion, and glycolysis in BC cells. SKA2 was verified as a direct target of miR‐140‐3p and its overexpression partially inhibited the suppressive effect of miR‐140‐3p restoration in BC cells. Additionally, circ_0008039 positively regulated SKA2 expression by sponging miR‐140‐3p. Consistently, silencing circ_0008039 restrained tumor growth via increasing miR‐140‐3p and decreasing SKA2. In conclusion, circ_0008039 downregulation suppressed BC cell proliferation, migration, invasion, and glycolysis partially through regulating the miR‐140‐3p/SKA2 axis, providing an important theoretical basis for treatment of BC.

Abbreviations

ANOVA

analysis of variance

BC

breast cancer

circRNAs

circular RNAs

DMSO

dimethyl sulfoxide

ECAR

extracellular acidification rate

ECL

enhanced chemiluminescence

FBS

fetal bovine serum

HK2

hexokinase II

MEGM

mammary epithelial growth medium

miR‐140‐3p

microRNA‐140‐3p

MTT

methylthiazolyldiphenyl‐tetrazolium bromide

PBS

phosphate‐buffered saline

PRKAR1B

protein kinase A regulatory subunit R1‐beta

SD

standard ± deviation

SKA2

spindle and kinetochore‐associated protein 2

     

A Phase II Study of Biodegradable Stents Plus Palliative Radiotherapy in Oesophageal Cancer

AimsSelf-expanding metal stents provide rapid improvement of dysphagia in oesophageal cancer but are associated with complications. The aim of the present study was to test the effectiveness of an alternative treatment of combining biodegradable stents with radiotherapy.Materials and methodsA Simon two-stage single-arm prospective phase II trial design was used to determine the efficacy of biodegradable stents plus radiotherapy in patients with dysphagia caused by oesophagus cancer who were unsuitable for radical treatment. Fourteen patients were recruited and data from 12 were included in the final analyses.ResultsFive of 12 patients met the primary end point: one stent-related patient death; four further interventions for dysphagia within 16 weeks of stenting (41.7%, 95% confidence interval 15.2–72.3%). The median time to a 10-point deterioration of quality of life was 2.7 weeks. Nine patients died within 52 weeks of registration. The median time to death from any cause was 15.0 weeks (95% confidence interval 9.6–not reached).ConclusionThe high re-intervention observed, which met the pre-defined early stopping criteria, meant that the suggested alternative treatment was not sufficiently effective to be considered for a larger scale trial design. Further work is needed to define the place of biodegradable stents in the management of malignant oesophageal strictures.     

Does a dedicated program for young breast cancer patients affect the likelihood of fertility preservation discussion and referral?

PurposeTo assess whether a dedicated program for young breast cancer patients, including a nurse navigator, improves the frequency of: a) fertility discussion documentation and b) fertility preservation (FP) referrals.MethodsA retrospective chart review and prospective survey were undertaken of breast cancer patients diagnosed at age 40 or younger between 2011 and 2013 who received adjuvant or neo-adjuvant chemotherapy at two academic cancer centers in Toronto, Canada. The Odette Cancer Centre (OCC) has a dedicated program for young breast cancer patients while Princess Margaret Cancer Centre (PM) does not. Patient demographics, tumor pathology, treatment and fertility discussion documentation prior to systemic chemotherapy administration were extracted from patient records. Prospective surveys were administered to the same cohort to corroborate data collected.ResultsEighty-one patient charts were reviewed at both OCC and PM. Forty-seven and 49 at OCC and PM returned surveys for a response rate of 58% and 60% respectively. Chart reviews demonstrated no difference in the frequency of fertility discussion documentation (78% versus 75% for OCC and PM, p = 0.71); however, surveys demonstrated higher rates of recall of fertility discussion at OCC (96% versus 80%, p = 0.02). A greater proportion of women were offered FP referrals at OCC, as observed in chart reviews (56% versus 41%, p = 0.09), and surveys (73% versus 51%, p = 0.04). Time to initiation of chemotherapy did not differ between women who underwent FP and those who did not.ConclusionA dedicated program for young breast cancer patients is associated with a higher frequency of FP referrals without delaying systemic therapy.     

Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial

BackgroundBrain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM.MethodsEighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response.ResultsThe lapatinib–temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09–20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82–3.37].ConclusionsThe lapatinib–temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.