Molecular intrinsic subtypes, genomic, and immune landscapes of BRCA-proficient but HRD-high ER-positive/HER2-negative early breast cancers.

PURPOSE: The vast majority of research studies that have described the links between DNA damage repair or homologous recombination deficiency (HRD) score, and tumor biology, have concerned either triple negative breast cancers or cancers with mutation of BRCA 1/2. We hypothesized that ER + /HER2- early breast tumors without BRCA 1/2 mutation could have high HRD score and aimed to describe their genomic, transcriptomic, and immune landscapes. PATIENTS AND METHODS: In this study, we reported BRCA 1/2 mutational status, HRD score, and mutational signature 3 (S3) expression, in all early breast cancer (eBC) subtypes from the TCGA database, with a particular focus in ER + /HER2-. In this subtype, bioinformatics analyses of tumor transcriptomic, immune profile, and mutational landscape were performed, according to HRD status. Overall survival (OS), progression free-interval (PFI), and variables associated with outcome were also evaluated. RESULTS: Among the 928 tumor samples analyzed, 46 harbored BRCA 1/2 mutations, and 606 were ER + /HER2- (of which 24 were BRCA 1/2 mutated). We found a subset of BRCA-proficient ER + /HER2- eBC, with high HRD score. These tumors displayed significantly different immune, mutational, and tumor molecular signatures landscapes, compared to BRCA-mutated and BRCA-proficient HRD-low tumors. Outcome did not significantly differ between these 3 groups, but biological factors associated with survival are not the same across the 3 entities. CONCLUSION: This study highlights possible novel biological differences among ER + /HER2- breast cancer related to HRD status. Our results could have important implications for translational research and/or the design of future clinical trials, but require prospective clinical evaluation.

Real-world prevalence, treatment and survival of "high risk" early breast cancer, with mandatory testing of gBRCA1/2 mutation according to the OlympiA trial inclusion criteria: Data from a population-based registry.

BACKGROUND: The results of the OlympiA study led to the approval of a PARP inhibitor (olaparib) as adjuvant treatment for early breast cancer (eBC) at high risk of relapse in patients with a germline BRCA1/2 mutation (gBRCAm). However, the proportion of patients in routine practice who meet the "high-risk" criteria applied in the OlympiA study, and for whom gBRCAm testing would now be mandatory, remains unknown. PATIENTS AND METHODS: In this population-based study, we use unique data from the French specialized Côte d'Or Breast and Gynecological Cancer Registry, to assess the real-life proportion, and long-term prognosis of patients treated for eBC between 2005 and 2015 with standard treatment, and at "high risk" of relapse according to the OlympiA trial criteria. RESULTS: We included 3483 patients treated for HER2-negative eBC (N = 380 with ER-, and N = 3103 with ER + tumor). We found N = 62 (1.8 %) patients with gBRCA1/2 mutations. A total of 494 patients (14.2 %) were classified as "high risk" according to the Olympia criteria; 55 % with ER-tumors, and 9.1 % with ER + tumors, respectively. Despite more intensive systemic treatments in "high risk" patients, 10-year overall survival was much worse in these "high risk" patients compared to the others: 60.1 % vs 83.8 % in ER-tumors, and 55.4 % vs 84.1 % in ER + tumors. Our estimates of net survival show an even greater difference. CONCLUSION: This study provides real-life insights into the prevalence and prognosis of patients with high-risk eBC, in a context where the approval of adjuvant olaparib requires careful reorganization of care, so as not to overlook a patient with gBRCAm who could benefit from adjuvant olaparib.

Taxane rechallenge during metastatic disease in HER-2 negative breast cancer patients: Clinical activity, tolerance and survival results.

BACKGROUND: Taxanes are major drugs for metastatic breast cancer (MBC) treatment, and are generally well tolerated, making them attractive for therapeutic reintroduction (rechallenge) during metastatic course. In view of the paucity of current literature, we questioned the usefulness of taxane rechallenge in a population of patients previously treated with taxanes in a metastatic setting. METHODS: From the local database of a French cancer center, we retrospectively identified 756 patients diagnosed with ER+/HER2-, or triple negative MBC, and treated between 2008 and 2021. Among them, 58 patients (7.8%) were rechallenged with taxanes. Clinical characteristics, response rates, and survival were retrospectively evaluated and compared to patients who received taxanes only once. RESULTS: Compared to non-rechallenged population, patients treated with taxane rechallenge were significantly younger, with better general status, and received more treatment. First taxane exposure led to better tumor response and was more frequently discontinued for reasons other than progression, compared to the non-rechallenged population. Taxane rechallenge led to an objective response rate of 27.6%, and a clinical benefit rate of 46.6%, with a median progression-free survival (PFS) of 5.7 months, and a median overall survival (OS) of 11.6 months. We also found a PFS2/PFS1 ratio >1.3 in 55.2% of the rechallenge population. CONCLUSION: Although only a minority of MBC patients are concerned, taxane rechallenge appears to be a pragmatic option with an acceptable tolerance, and good efficacy, especially when these drugs have shown clinical activity earlier in the disease course, and/or have been stopped for reasons other than progression.

Clinical Utility of Genomic Tests Evaluating Homologous Recombination Repair Deficiency (HRD) for Treatment Decisions in Early and Metastatic Breast Cancer.

Breast cancer is the most frequently occurring cancer worldwide. With its increasing incidence, it is a major public health problem, with many therapeutic challenges such as precision medicine for personalized treatment. Thanks to next-generation sequencing (NGS), progress in biomedical technologies, and the use of bioinformatics, it is now possible to identify specific molecular alterations in tumor cells-such as homologous recombination deficiencies (HRD)-enabling us to consider using DNA-damaging agents such as platinum salts or PARP inhibitors. Different approaches currently exist to analyze impairment of the homologous recombination pathway, e.g., the search for specific mutations in homologous recombination repair (HRR) genes, such as BRCA1/2; the use of genomic scars or mutational signatures; or the development of functional tests. Nevertheless, the role and value of these different tests in breast cancer treatment decisions remains to be clarified. In this review, we summarize current knowledge on the clinical utility of genomic tests, evaluating HRR deficiency for treatment decisions in early and metastatic breast cancer.

Pathologic and immunohistochemical prognostic markers in residual triple-negative breast cancer after neoadjuvant chemotherapy.

Background: The persistence of residual tumour after neoadjuvant chemotherapy (NAC) in localised triple-negative breast cancer (TNBC) is known to have a negative prognostic value. However, different degrees of expression of some immunohistochemical markers may correlate with different prognoses. Methods: The expression of biomarkers with a known prognostic value, i.e., cytokeratin 5/6 (CK5/6), androgen receptor (AR), epidermal growth factor receptor (EGFR) proliferation-related nuclear antigen Ki-67, human epidermal growth factor receptor 2 (HER2), protein 53 (p53), forkhead box protein 3 (FOXP3), and cluster differentiation 8 (CD8), was analysed by immunohistochemistry in 111 samples after NAC in non-metastatic TNBC patients addressed to Georges-François Leclerc Cancer Centre Dijon, France. Clinical and pathological variables were retrospectively collected. Cox regression was used to identify immunohistochemical (IHC) and clinicopathological predictors of event-free survival (EFS) (relapse or death). Results: Median age was 50.4 years (range 25.6-88.3), 55.9% (n = 62) were non-menopausal, 70 (63.1%) had stage IIA-IIB disease. NAC was mostly sequential anthracycline-taxanes (72.1%), and surgical intervention was principally conservative (51.3%). We found 65.7% ypT1, 47.2% lymph node involvement (ypN+), and 29.4% lymphovascular invasion (LVI). Most residual tumours were EGFR >110 (H-score) (60.5%, n = 66), AR ≥4% (53.2%, n = 58), p53-positive mutated (52.7%, n = 58), CD8 ≥26 (58.1%, n = 61), FOXP3 ≥7 (51.4%, n = 54), more than half in the stroma, and 52.3% (n = 58) HER2 score 0. After a median follow-up of 80.8 months, 48.6% had relapsed. Median EFS was 62.3 months (95% CI, 37.2-not reached (NR)). Factors independently associated with poor EFS were AR-low (p = 0.002), ypN+ (p < 0.001), and LVI (p = 0.001). Factors associated with lower overall survival (OS) were EGFR-low (p = 0.041), Ki-67 high (p = 0.024), and ypN+ (p < 0.001). Conclusion: Post-NAC residual disease in TNBC showed biomarkers specific to a basal-like subtype and markers of lymphocyte infiltration mostly present in the stroma. Prognostic markers for EFS were AR, LVI, and ypN and warrant further validation in a prognostic model.

Pathologic complete response and survival in HER2-low and HER2-zero early breast cancer treated with neoadjuvant chemotherapy.

BACKGROUND: Breast cancers without HER2 amplification but still expressing this membrane protein constitute a new entity called HER2-low tumors. It is important to characterize them in terms of sensitivity to treatment and prognosis. PATIENTS AND METHODS: To investigate chemosensitivity and long-term prognosis of HER2-low early breast cancer (eBC), compared to HER2-0 tumors, we retrospectively retrieved clinicopathological characteristics, response to treatment, and survival data from 511 patients treated for eBC with neoadjuvant chemotherapy (NAC) in a French cancer center between 2007 and 2018. Factors associated with the achievement of pathologic complete response (pCR) and survival were studied among hormone receptor positive (HR+) and negative (HR-) eBC. RESULTS: A total of 280 HR+ (61% HER2-low), and 231 HR- (28% HER2-low) eBC were included. We found classical clinicopathological factors usually associated with chemosensitivity and prognosis, in both HR+ and HR- eBC. By uni- and multivariable analysis, HER2 status (low vs 0) was not independently associated with pCR, either in HR+ or HR- eBC. Relapse free (RFS) and overall survival (OS) were not significantly different between HER2-low and HER2-0 among HR+ tumors. In contrast, among HR- negative tumors, RFS and OS were slightly better in HER2-0 eBC by univariable but not by multivariable analysis. CONCLUSIONS: In eBC patients treated with NAC, taking into account HR expression subtype and other current clinicopathological features, HER2-low tumors did not appear to have different chemosensitivity or prognosis, compared to their HER2-0 counterparts.

Efficacy of Chemotherapy Plus Bevacizumab in Recurrent Glioblastoma Multiform: A Real-life Study.

BACKGROUND/AIM: Bevacizumab and chemotherapy are used in glioblastoma multiforme (GBM) relapse. However, the choice of chemotherapeutic agent remains an open question and this study aimed to evaluate the efficacy and safety of different combinations. PATIENTS AND METHODS: Between June 2005 and August 2020, all patients treated with chemotherapy plus bevacizumab (BVZ) for recurrent glioblastoma in the Georges-François Leclerc Cancer Center, Dijon, France were included in this retrospective comparative study. The primary objective was progression-free survival (PFS) and as secondary objectives, overall survival (OS), disease control rate (DCR), and safety were investigated. Factors associated with response were also analyzed. RESULTS: A total of 160 patients were screened: 100 received fotemustine plus BVZ (62%) and 62 (38%) received another cytotoxic agent plus BVZ: 35 (22%) irinotecan (IRI), 18 (11%) temozolomide (TEM), and 7 (4%) lomustine (LOM). In the whole population, median PFS was 4.47 months, median OS was 9 months, and 3-month DCR was 51%. Regarding survival according to treatment, median OS was significantly lower in the fotemustine group compared to that in other cytotoxic agents: 7.3 vs. 19.9 months. In the fotemustine group, steroids use at baseline and low Karnofsky performance status were associated with poor median OS. Grade 3-4 adverse events were found in 21.9%, with no difference between groups, but 7 patients had grade 5 adverse events in the fotemustine group. CONCLUSION: Using real-life data, this study showed lower efficacy of fotemustine and bevacizumab, as compared to IRI or TEM or LOM-BVZ combinations.

Optimization of G-CSF dosing schedule in patients treated with eribulin: a modeling approach.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSF) are commonly given to limit chemotherapy-induced neutropenia, but, in case of weekly chemotherapy such as eribulin, their administration schedules remain empirical. OBJECTIVES: This pharmacokinetic/pharmacodynamic (PK/PD) study was conducted to establish the effect of different G-CSF regimens on neutropenia's incidence for patients treated by eribulin, to propose an optimal G-CSF dosing schedule. METHODS: A population PK/PD model was developed to describe absolute neutrophil counts' (ANC) time course in 87 cancer patients receiving eribulin. The structural model considered ANC dynamics, neutropenic effect of eribulin and stimulating effect of G-CSF. Final model estimates were used to calculate neutropenia's incidence following different G-CSF dosing schedules for 1000 virtual subjects. RESULTS: The final model successfully described most of the ANC time course for all patients. Simulations showed that a single G-CSF administration 48 h after each eribulin injection reduced the risk of severe neutropenia from 29.7 to 5.2%. Five days of G-CSF only after the second eribulin injection or no G-CSF administration induces similar incidence of neutropenia. CONCLUSION: Simulations showed a single G-CSF administration 48 h after the end of each eribulin injection seems to be the optimal schedule to reduce eribulin-induced neutropenia. However, the new administration scheme should be tested in real life to evaluate its pertinence. TRIAL REGISTRATION: Eudract 2015-001753-32, 2015/01/26.

Efficacy of platinum-based chemotherapy in metastatic breast cancer and HRD biomarkers: utility of exome sequencing.

Metastatic breast cancer (MBC) is frequently managed by platinum-based chemotherapy during the disease course. The real benefit of these treatments is uncertain at advanced stages of the disease and in non-triple-negative subtypes. Since homologous recombination deficiency (HRD) could inform about tumor sensitivity to DNA-damaging agents, we aimed to determine biomarkers of genomic instability, and their link with platinum efficacy. In this single-center study, we report BRCA1/2 mutational status, HRD score and signature 3 levels, all obtained by tumor exome sequencing, in 86 patients with various subtypes of MBC and who received platinum-based chemotherapy. Overall response rate, disease control rate, PFS and PFS2/PFS1 ratio were evaluated to assess platinum-based chemotherapy efficacy. Among the 86 tumor samples analyzed, 7 harbored BRCA1/2 mutations. We found a subset of BRCA-proficient MBC with high HRD score or high S3 levels, comparable to BRCA-mutated tumors. However, these patients with high HRD score or high S3 tumor level do not seem to benefit more from platinum-based chemotherapy than the others, in terms of response rates and/or PFS, regardless of BC molecular subtype. By multivariate analysis, only the absence of liver metastases was independently associated with significantly better PFS on platinum-based chemotherapy. However, some of our exploratory analyses reveal that certain methods, when optimized, seem to associate with platinum benefit. Tumor exome sequencing methodology for quantifying HRD has to be approached systematically, and further validated and standardized prior to its clinical use. Further studies are warranted to confirm these results to guide platinum use in MBC.

Parallel evolution and differences in seroprevalence of SARS-CoV-2 antibody between patients with cancer and health care workers in a tertiary cancer centre during the first and second wave of COVID-19 pandemic: canSEROcov-II cross-sectional study.

BACKGROUND: Patients with cancer are a population at high risk of severe infection from SARS-CoV-2. Patients with cancer regularly attend specialised healthcare centres for management and treatment, where they are in contact with healthcare workers (HCWs). Numerous recommendations target both patients with cancer and HCWs to minimise the spread of SARS-CoV-2 during these interactions. OBJECTIVE: To investigate the parallel evolution of the COVID-19 epidemic in these 2 populations over time, we studied the seroprevalence of anti-SARS-CoV-2 antibodies after both the first and second waves of the pandemic, and in both cancer patients and HCWs from a single specialised anti-cancer centre. Factors associated with seropositivity were identified in both populations. METHODS: We conducted a cross-sectional study after the second wave of the COVID pandemic in France. All participants were invited to undergo serological testing for SARS-CoV-2 and complete a questionnaire collecting data about their working conditions (for HCWs) or medical management (for patients) during this period. Results after the second wave were compared to those of a previous study among 1011 patients with cancer and 663 HCWs performed in the same centre after the first wave, using the same evaluations. FINDINGS: We included 502 HCWs and 507 patients with cancer. Seroprevalence of anti-SARS-CoV-2 antibodies was higher after the second wave than after the first wave in both HCWs (15.1% versus 1.8%; p < 0.001), and patients (4.1% versus 1.7%; p = 0.038). By multivariate analysis, the factors found to be associated with seropositivity after the second wave for HCWs were: working in direct patient care (p = 0.050); having worked in a dedicated COVID-19 unit (p = 0.0036); contact with a person with COVID-19-positive in the workplace (p = 0.0118) or outside of the workplace (p = 0.0297). Among patients with cancer, only a contact with someone who tested positive for COVID-19 was found to be significantly associated with positive serology. The proportion of reported contacts with individuals with COVID-19-positive was significantly lower among patients with cancer than among HCWs (7.6% versus 40.7%, respectively; p < 0.0001) INTERPRETATION: Between the first and second waves of the epidemic in France, the seroprevalence of anti-SARS-CoV-2 antibodies increased to a lesser extent among patients with cancer than among their HCWs, possibly due to better self-protection, notably social distancing. The risk factors for infection identified among HCWs plead in favour of numerous intra-hospital contaminations, especially for HCWs in contact with high-risk patients. This underlines the compelling need to pursue efforts to implement strict hygiene and personal protection measures (including vaccination) to protect HCWs and patients with cancer.

Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients.

Palbociclib is an oral CDK4/6 inhibitor indicated in HR+/HER2- advanced or metastatic breast cancer in combination with hormonotherapy. Its main toxicity is neutropenia. The aim of our study was to describe the kinetics of circulating neutrophils from real-life palbociclib-treated patients. A population pharmacokinetic (popPK) model was first constructed to describe palbociclib pharmacokinetic (PK). Individual PK parameters obtained were then used in the pharmacokinetic/pharmacodynamic (PK/PD) model to depict the relation between palbociclib concentrations and absolute neutrophil counts (ANC). The models were built with a population of 143 patients. Palbociclib samples were routinely collected during therapeutic drug monitoring, whereas ANC were retrospectively retrieved from the patient files. The optimal popPK model was a mono-compartmental model with a first-order absorption constant of 0.187 h-1 and an apparent clearance Cl/F of 57.09 L (32.8% of inter individuality variability (IIV)). The apparent volume of distribution (1580 L) and the lag-time (Tlag: 0.658 h) were fixed to values from the literature. An increase in creatinine clearance and a decrease in alkaline phosphatase led to an increase in palbociclib Cl/F. To describe ANC kinetics during treatment, Friberg's PK/PD model, with linear drug effect, was used. Parameters estimated were Base (2.92 G/L; 29.6% IIV), Slope (0.0011 L/µg; 28.8% IIV), Mean Transit Time (MTT; 5.29 days; 17.9% IIV) and γ (0.102). The only significant covariate was age on the initial ANC (Base), with lower ANC in younger patients. PK/PD model-based simulations show that the higher the estimated CressSS (trough concentration at steady state), the higher the risk of developing neutropenia. In order to present a risk lower than 20% to developing a grade 4 neutropenia, the patient should show an estimated CressSS lower than 100 µg/L.

Seroprevalence of SARS-CoV-2 among the staff and patients of a French cancer centre after first lockdown: The canSEROcov study.

BACKGROUND: In view of the potential gravity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection for patients with cancer, epidemiological data are vital to assess virus circulation among patients and staff of cancer centres. We performed a prospective study to investigate seroprevalence of SARS-CoV-2 antibodies among staff and patients with cancer at a large cancer centre, at the end of the period of first national lockdown in France and to determine factors associated with the risk of SARS-CoV-2 infection. METHODS: After the first lockdown, all medical and non-medical staff, as well as all patients attending the medical oncology department were invited to undergo serological testing for SARS-CoV-2 between 11 May and 30 June 2020. All participants were also invited to complete a questionnaire collecting data about their living and working conditions, and for patients, medical management during lockdown. FINDINGS: A total of 1,674 subjects (663 staff members, 1011 patients) were included. Seroprevalence was low in both staff (1.8%) and patients (1.7%), despite more features of high risk for severe forms among patients. None of the risk factors tested in our analysis (working or living conditions, comorbidities, management characteristics during lockdown) was found to be statistically associated with seroprevalence in either staff or patients. There was no significant difference in the proportion of symptomatic and asymptomatic subjects between staff and patients. Only fever, loss of smell, and loss of taste were significantly more frequent among seropositive patients, in both staff and patients. INTERPRETATION: We report very low seroprevalence of antibodies against SARS-CoV-2 in the staff (caregiving and non-caregiving) and patients of a large cancer care centre in which strict hygiene, personal protection, and social distancing measures were implemented.

Pathologic Response After Weekly Paclitaxel versus Docetaxel in Operable Breast Cancer.

INTRODUCTION: Weekly paclitaxel (Ptx) and q3w docetaxel (Dtx) are equivalent in adjuvant breast cancer treatment. Weekly Ptx is better tolerated than q3w Dtx and became the first choice in daily practice, even preoperatively. METHODS: To compare the efficacy and safety of the two regimens, a retrospective analysis was performed in breast cancer patients (pts) referred for neoadjuvant, sequential, taxane-containing chemotherapy to the Institute of Oncology and Oncofort Clinic, Bucharest, between 2008 and 2017. RESULTS: Forty-seven cases were eligible, median age was 56 years (34-73 years), mainly stage IIIA-B (53.2%, 25 pts) and ductal invasive (70.2%, 33 pts) of which 24 pts (51%) received q3w Dtx and 23 pts (48.9%) weekly Ptx. The histological response rates were 62.5% (15 pts) and 73.7% (17 pts) (p=0.47), average dose-intensity was 87.7% and 96.7% (p=0.002) and grade III-IV toxicity rate was 12.5% and 13% (p=0.64), respectively. Pathologic response was correlated with immunophenotype, PgR expression, tumor size and backbone chemotherapy (p<0.05). DISCUSSION: Our study showed an improved efficacy of taxane's weekly administration, probably due to a better tolerance and a lower rate of dose-impairing toxicities.

Real-world Evaluation of Oral Vinorelbine in the Treatment of Metastatic Breast Cancer: An ESME-MBC Study.

BACKGROUND/AIM: Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug. PATIENTS AND METHODS: Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described. RESULTS: A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months. CONCLUSION: Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports.

Rare Pelvic Malignant Tumors in Adults: Treatment Features and Clinical Outcome in Nonmetastatic Disease (Single Institution Experience).

BACKGROUND: Nearly 200 cancers repertories are rare, and more than 20% are pelvic neoplasia. Diagnosis and treatment are challenging, even in reference centers, and survival is influenced by the aggressiveness of certain histologies and absence of a standard of care. PATIENTS AND METHODS: The authors report the results of a retrospective analysis of patients that attended the Institute of Oncology, Bucharest, between 2004 and 2015, for nonmetastatic pelvic malignant tumor treatment and follow-up. The outcomes are compared between the rare and common histology groups. RESULTS: Of the 60 cases analyzed, 17 patients (28.33%) bore a rare tumor, 33 (55%) were women, and the median age was 59 years. The majority was concerned by bladder (41.66%, 25 patients) and cervix (23.33%, 14 patients) neoplasms. For a median follow-up of 27.5 months, relapse was registered in 27 patients (45%), of whom 9 (33.33%) were from the rare group (53% of this subpopulation). The highest relapse rates were recorded in patients with rare bladder tumors (66.7%, 4 patients) compared with 42.1% (8 patients) in the common group (p = 0.294) and in prostate localization (66.7%, 2 patients) compared with 16.7% (1 patient) (p = 0.134). Estimated median relapse-free survival (RFS) was 60, 12 months in the rare group and 67 months for common tumors. CONCLUSIONS: In nonmetastatic rare pelvic tumor patients, the outcome was found to be poorer than in those concerned by common histologies stratified by organ. A higher rate of relapse and the lowest median RFS were observed in bladder and prostatic cancers.

Potential clinically useful prognostic biomarkers in triple-negative breast cancer: preliminary results of a retrospective analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis, even in its early stages. In the absence of postoperative targeted treatments, intensive adjuvant chemotherapy regimens are proposed. For those favorable histologies, such as apocrine and adenoid cystic carcinoma, which frequently belong to TNBC, aggressive treatments are unnecessary. PATIENTS AND METHODS: We retrospectively analyzed 631 cases of breast cancer, primary operated curatively, and followed up at our institution for at least 36 months to identify the bio-markers assessable by immunohistochemistry, to be proposed as prognostic score for tailoring adjuvant treatment to TNBC patients. RESULTS: The triple-negative phenotype was found in 85 patients (13.5%). Over a mean followup of 55.7 months, relapses occurred in 106 patients (16.8%), of which 18 (2.8%) were TNBC. Recurrence was directly correlated with Ki67 and cytokeratin 5/6 (CK5/6) immunoreactivity in all breast cancer patients (P=0.005), but only marginally with CK5/6 and epithelial cadherin (E-cad) expression in TNBC patients (P=0.07). Mean event-free survival (EFS) in TNBC patients was 85.52 months compared with 100.4 months in non-TNBC patients (P=0.228). The EFS of CK5/6-negative triple-negative patients was 68.84 months compared with 98.84 months in those who were CK5/6 positive (HR =5.08; P=0.038). EFS differed among patients identified as double-positive for E-cad and CK5/6 (83.87 months), those expressing E-cad or CK5/6 (64.23 months), and those negative for both biomarkers (39.64 months). CONCLUSION: These preliminary results suggest that CK5/6 and E-cad are possible core biomarkers for a cost-effective prognostic evaluation of primary operable TNBC patients.

Good Prognosis Went Badly: Fulminant Evolution of a 29-Year-Old Patient with Verrucous Carcinoma of the Cervix.

Verrucous carcinoma (VC) is a very rare variant of squamous cell carcinoma of the cervix, difficult to point out in histology because of its benign appearance. We present the case of a 29-year-old woman with a locally advanced cervical VC who underwent radiotherapy followed by radical hysterectomy. After local relapse and despite pelvic exenteration, her condition deteriorated. Treatment of choice in VC is surgery, because of the risk of anaplastic transformation under irradiation, raising the chances of distant spread and converting this rather benign-like type of cancer to an aggressive cancer.

Current Targeted Therapies in HER2-Positive Gastric Adenocarcinoma.

Gastric cancer is one of the most common types of cancer in the world, usually diagnosed at an advanced stage. Despite the advances in specific anticancer agents' development, the survival rates remain modest, even in early stages. In 15%-20% of cases, the human epidermal growth factor receptor 2 (HER2) overexpression was identified. We conducted a general review to summarize the progress that has been made in the targeted treatment of HER2-positive esogastric junction or gastric adenocarcinoma. According to our findings, trastuzumab is the only validated anti-HER2 agent in locally advanced or metastatic disease and its adjuvant effectiveness is assessed in a RTOG phase III study. In a previously treated advanced disease, the maytansine derivate TDM 1 failed to be approved as a second-line regimen, and the tyrosine kinase inhibitor, lapatinib, shows modest results. The antiangiogenics have not been analyzed in specific populations and targeting the mesenchymal-epithelial transition factor (MET) receptor, overexpressed in up to 46% of the advanced disease, seems encouraging. Regarding the checkpoint inhibitors, based on KEYNOTE 059 multilevel ongoing trial, stratified according to the HER2 and programmed death-ligand (PD-L) 1 status, pembrolizumab was approved for third-line treatment of gastric or gastroesophageal junction adenocarcinoma.