mutations are grouped in activating
-independent signaling as monomers (class 1-V600E) or as dimers (class 2-codons 597/601), and
-dependent with impaired kinase activity (class 3-codons 594/596). ...Although clinical, pathologic, and molecular features of
-mutated metastatic colorectal cancer (mCRC) are well known, limited data are available from the two other classes.
Data from 117 patients with
(92 class 1, 12 class 2, and 13 class 3)-mutated mCRC were collected. A total of 540
wt mCRCs were included as control. IHC profiling was performed to determine the consensus molecular subtypes (CMS), cytokeratin 7/20 profiles, tumor-infiltrating lymphocyte infiltration, and BM1/BM2 categorization. Overall survival (OS) and progression-free survival were evaluated by Kaplan-Meier and log-rank test.
Class 3
-mutated mCRC was more frequently left sided (
= 0.0028), pN0 (
= 0.0159), and without peritoneal metastases (
= 0.0176) compared with class 1, whereas class 2 cases were similar to class 1. Hazard ratio for OS, as compared with
wt, was 2.38 95% confidence interval (CI), 1.61-3.54 for class 1, 1.90 (95% CI, 0.85-4.26) for class 2, and 0.93 (95% CI, 0.51-1.69) for class 3 (
< 0.0001). Class 2 and 3 tumors were all assigned to CMS2-3. A higher median CD3/CD8-positive lymphocyte infiltration was observed in
-mutated class 2 (
= 0.033) compared with class 3 cases.
For the first time, different clinical and pathologic features and outcome data were reported according to the three
mutation classes in mCRC. Specific targeted treatment strategies should be identified in the near future for such patients.
Objectives
To investigate the role of automated breast volume scanner (ABVS) compared to handheld ultrasound (HHUS) and contrast-enhanced magnetic resonance imaging (CE-MRI) in the early detection of ...patients with locally advanced breast cancer who are more likely to reach a complete pathological response (pCR) during neoadjuvant chemotherapy (NAC).
Methods
A single-institution prospective study was performed in patients with histological diagnosis of invasive breast cancer, eligible for NAC, and who were to undergo surgery in our Hospital. Imaging examinations with ABVS, HHUS and CE-MRI were performed at diagnosis (basal time) and after 3 months of chemotherapy (middle time). The tumor size of each lesion was measured at the basal and middle times, and the dimensional variation was reported. Based on this, patients were divided dichotomously by the median value, obtaining “good responders” (goodR)
versus
“poor responders” (poorR). The results were correlated with the histological assessment (pCR
versus
No-pCR) with the use of the intergroup comparison of categorical data (Fisher's exact test).
Result
A total of 21 patients were included; 5 obtained a pCR (23%). Both the ABVS and the CE-MRI found all 5 patients with pCR in the group of goodR (10 patients), while none of the poorR (11 patients) obtained a pCR correlation was statistically significant (
p
0.01). In the HHUS, goodR (10 patients) 1 obtained a pCR while in the poorR (11 patients) 4 obtained a pCR correlation not statistically significant (
p
0.31).
Conclusions
ABVS could be a useful tool, appearing to be more reliable than HHUS, and as accurate as CE-MRI, in early detection of patients who could reach a pCR after NAC.
The efficacy and safety of the combination of endocrine therapy (ET) and CDK4/6 inhibitors for patients with hormone receptor (HR)-positive HER2-negative metastatic breast cancer (BC) presenting with ...visceral crisis or life-threatening conditions represent a challenge for daily clinical practice. Indeed, the peculiarity of this clinical presentation (signs and symptoms of rapidly progressive disease) does not allow to include such patients in a trial aiming for drug approval. On the basis of the scientific evidence available so far, chemotherapy represents the standard of care according to guidelines, on the basis of the more rapid activity in comparison with ET alone. Besides, the combination of ET and CDK4/6 inhibitors have demonstrated in clinical trials to have clinically impactful activity in a short time, thus suggesting a potential role in advanced tumors that require rapid response. Herein, we report the clinical history of a young woman with HR-positive HER2-negative metastatic BC and a pancytopenia due to carcinomatosis of the bone marrow receiving letrozole and leuprorelin plus the CDK4/6 inhibitor palbociclib, who significantly derived clinical benefit from treatment. Considering that these peculiar cases are excluded from clinical trials, the estimation of the magnitude of the benefit of the newer ET combination may potentially represent a practical question for large case series and real-world studies.
Breast cancer is the leading cause of death in the female population and despite significant efforts made in diagnostic approaches and treatment strategies adopted for advanced breast cancer, the ...disease still remains incurable. Therefore, development of more effective systemic treatments constitutes a crucial need. Recently, several clinical trials were performed to find innovative predictive biomarkers and to improve the outcome of metastatic breast cancer through innovative therapeutic algorithms. In the pathogenesis of breast cancer, the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of rapamycin (mTOR) axis is a key regulator of cell proliferation, growth, survival, metabolism, and motility, making it an interest and therapeutic target. Nevertheless, the PI3K/AKT/mTOR cascade includes a complex network of biological events, needing more sophisticated approaches for their use in cancer treatment. In this review, we described the rationale for targeting the PI3K pathway, the development of PI3K inhibitors and the future treatment directions of different breast cancer subtypes in the metastatic setting.
Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic ...backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ patients develop resistance to ET within their lifetime, ultimately leading to disease recurrence and limited clinical benefit. The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to ET have remarkably improved the outcome of patients with HR+ advanced breast cancer (ABC) compared with anti-estrogens alone, by targeting the cell-cycle machinery and overcoming some aspects of endocrine resistance. However, which patients are the better candidates for these drugs, which are the main characteristics for a better selection of patients or if there are predictive biomarkers of response, is still unknown. In this review we reported the mechanism of action of CDK4/6 inhibitors as well as their potential mechanism of resistance, their implications in clinical practice and the forthcoming strategies to enhance their efficacy in improving survival and quality of life of patients affected with HR+, HER2-, ABC.
The role of surgical resection of liver metastases in patients with breast cancer liver metastasis (BCLM) remains controversial. A systematic review and meta-analysis of prognostic factors related to ...survival after BCLM resection was performed.
An electronic search of relevant publications was performed. Pooled outcome measures were expressed as hazard ratios (HRs), including 95% confidence interval values (95% CIs), and calculated through a random-effects model. Heterogeneity was tested through the I
index.
Thirty-five publications reported analyses on prognostic factors and survival. A total of 2782 patients who underwent liver resection for BCLM were included. Positive axillary lymph nodes at breast cancer diagnosis were an unfavorable survival factor (HR 1.74, 95% CI 1.25 to 2.41, I
= 0%). Cumulative predictive factor HRs (multiple liver metastases, size of the metastases, short interval between primary tumor and onset of liver disease) related to the BCLM pattern were 1.32 (95% CI 1.17 to 1.48, I
= 71%) and 1.51 (95% CI 1.15 to 1.98, I
= 76%) for surgical and pathological features (resection margin and presence of extrahepatic disease), respectively.
Resection of BCLM may provide a survival benefit for selected patients. For better long-term results, surgical selection should consider both primary tumor and BCLM features such as negative axillary lymph nodes at breast resection, a single hepatic lesion, a time longer than 24 months between breast and hepatic diagnosis, and a realizable R0 liver resection. However, the high heterogeneity among studies suggests the need for an RCT to validate the present findings.
The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and ...development of new target therapies, oligometastatic and oligoprogressive settings are even more common—paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.
Cancer treatment-related adverse events (AEs) are sometimes associated with outcomes for cancer patients, especially with the newest therapies such as target therapy and immunotherapy. A few years ...ago, the first-line therapy for hormone-receptor-positive metastatic breast cancer (mBC) patients has been deeply changed by the introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors, and now, we are improving our knowledge about their AEs and significance in clinical practice. Here, we report our experience with two cases of vitiligo-like lesions that occur early during treatment with ribociclib. We tried to change the CDK4/6 inhibitor for one patient, but the skin reaction persisted. Both patients retained only the endocrine therapy alone and had an unexpected durable progression-free survival (PFS). Some data on skin toxicities, including vitiligo-like lesions by CDK4/6 inhibitors, have recently been reported in the literature, but for the first time, we highlight a possible correlation with improved survival outcomes of patients. Uncovering the etiology of this toxicity, verifying the involvement of the immune system, and demonstrating a possible positive impact in survival represent an intriguing research objective for the near future.
The aim of this study was to compare outcomes of immediate prosthetic breast reconstruction (IPBR) using traditional submuscular (SM) positioning of implants versus prepectoral (PP) positioning of ...micropolyurethane-foam-coated implants (microthane) without further coverage.
We retrospectively reviewed the medical records of breast cancer patients treated by nipple-sparing mastectomy (NSM) and IPBR in our institution during the two-year period from January 2018 to December 2019. Patients were divided into two groups based on the plane of implant placement: SM versus PP.
177 patients who received IPBR after NSM were included in the study; implants were positioned in a SM plane in 95 patients and in a PP plane in 82 patients. The two cohorts were similar for mean age (44 years and 47 years in the SM and PP groups, respectively) and follow-up (20 months and 16 months, respectively). The mean operative time was 70 min shorter in the PP group. No significant differences were observed in length of hospital stay or overall major complication rates. Statistically significant advantages were observed in the PP group in terms of aesthetic results, chronic pain, shoulder dysfunction, and skin sensibility (
< 0.05), as well as a trend of better outcomes for sports activity and sexual/relationship life. Cost analysis revealed that PP-IPBR was also economically advantageous over SM-IPBR.
Our preliminary experience seems to confirm that PP positioning of a polyurethane-coated implant is a safe, reliable and effective method to perform IPBR after NSM.
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