Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: BRCA1 or BRCA2-mutated breast cancers are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors and platinum agents owing to deficiency in homologous recombination repair of DNA damage. In this trial, we compared veliparib versus placebo in combination with carboplatin and paclitaxel, and continued as monotherapy if carboplatin and paclitaxel were discontinued before progression, in patients with HER2-negative advanced breast cancer and a germline BRCA1 or BRCA2 mutation. METHODS: BROCADE3 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 147 hospitals in 36 countries. Eligible patients (aged ≥18 years) had deleterious germline BRCA1 or BRCA2 mutation-associated, histologically or cytologically confirmed advanced HER2-negative breast cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received up to two previous lines of chemotherapy for metastatic disease. Patients were randomly assigned (2:1) by interactive response technology by means of permuted blocks within strata (block size of 3 or 6) to carboplatin (area under the concentration curve 6 mg/mL per min intravenously) on day 1 and paclitaxel (80 mg/m2 intravenously) on days 1, 8, and 15 of 21-day cycles combined with either veliparib (120 mg orally twice daily, on days -2 to 5) or matching placebo. If patients discontinued carboplatin and paclitaxel before progression, they could continue veliparib or placebo at an intensified dose (300 mg twice daily continuously, escalating to 400 mg twice daily if tolerated) until disease progression. Patients in the control group could receive open-label veliparib monotherapy after disease progression. Randomisation was stratified by previous platinum use, history of CNS metastases, and oestrogen and progesterone receptor status. The primary endpoint was investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy analyses were done by intention to treat, which included all randomly assigned patients with a centrally confirmed BRCA mutation, and safety analyses included all patients who received at least one dose of velilparib or placebo. This study is ongoing and is registered with ClinicalTrials.gov, NCT02163694. FINDINGS: Between July 30, 2014, and Jan 17, 2018, 2202 patients were screened, of whom 513 eligible patients were enrolled and randomly assigned. In the intention-to-treat population (n=509), 337 patients were assigned to receive veliparib plus carboplatin-paclitaxel (veliparib group) and 172 were assigned to receive placebo plus carboplatin-paclitaxel (control group). Median follow-up at data cutoff (April 5, 2019) was 35·7 months (IQR 24·9-43·6) in the veliparib group and 35·5 months (23·1-45·9) in the control group. Median progression-free survival was 14·5 months (95% CI 12·5-17·7) in the veliparib group versus 12·6 months (10·6-14·4) in the control group (hazard ratio 0·71 [95% CI 0·57-0·88], p=0·0016). The most common grade 3 or worse adverse events were neutropenia (272 [81%] of 336 patients in the veliparib group vs 143 [84%] of 171 patients in the control group), anaemia (142 [42%] vs 68 [40%]), and thrombocytopenia (134 [40%] vs 48 [28%]). Serious adverse events occurred in 115 (34%) patients in the veliparib group versus 49 (29%) patients in the control group. There were no study drug-related deaths. INTERPRETATION: The addition of veliparib to a highly active platinum doublet, with continuation as monotherapy if the doublet were discontinued, resulted in significant and durable improvement in progression-free survival in patients with germline BRCA mutation-associated advanced breast cancer. These data indicate the utility of combining platinum and PARP inhibitors in this patient population. FUNDING: AbbVie.

The influence of cognitive schemas on the mixed anxiety-depressive symptoms of breast cancer patients.

BACKGROUND: The surgical treatment of breast cancer involves various psychological consequences, which differ according to individual characteristics. Our study aimed to identify the role that cognitive schemas had in triggering anxiety and depressive symptoms in patients diagnosed with breast cancer that underwent oncological and plastic surgery treatment. METHODS: 64 female patients, diagnosed with breast cancer from an Oncology and Plastic Surgery Hospital, were selected to participate in this study between March-June 2018. They were divided into two groups: I. 28 patients who underwent mastectomy surgery; II. 36 patients, who required mastectomy and, subsequently, also chose to undergo breast reconstruction surgery. For the purposes of evaluating a possible change in mental health status, we employed two assessment scales: the Young Cognitive Schema Questionnaire - Short Form 3 (YSQ-S3) and the Romanian version of the Depression Anxiety Stress Scale - 21 (DASS-21R). RESULTS: Participants who underwent mastectomy and subsequent breast reconstruction surgery employed cognitive schemas that did not generate symptoms of depression or anxiety. In contrast, the cognitive schemas found in women who refused reconstructive breast surgery were significantly correlated with the presence of anxiety-depressive symptoms. The cognitive schema domain of 'disconnection and rejection' correlated uncertainly with the presence of anxiety-depressive symptoms for the group with breast reconstruction (Spearman's ρ = 0.091, p = 0.644), while for the other group the correlation was moderate-strong (Spearman's ρ = 0.647, p <  0.01). Negative emotional schemas were significantly correlated with the presence of anxiety-depressive symptoms (Spearman's ρ = 0.598, p <  0.01) in the group of participants without reconstructive surgery. CONCLUSION: A correct identification of dysfunctional cognitive schemas and coping mechanisms at the commencement of the combined treatment in breast cancer patients could serve as an indicator for the evolution of their mental health, therefore assisting professionals in establishing the most suitable psychological, psychotherapeutic and psychiatric intervention plan.

NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron.

PURPOSE: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. METHODS: This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. RESULTS: Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. CONCLUSIONS: NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

Effectiveness and safety profile of ipilimumab therapy in previously treated patients with unresectable or metastatic melanoma - the Romanian Patient Access Program.

PURPOSE: The Romanian Patient Access Program (Ro-PAP, CA 184-427), part of the European Expanded Access Program (EAP), was developed to evaluate the effectiveness and safety profile ipilimumab in previously treated patients with advanced melanoma (unresectable or metastatic melanoma). The objective of our retrospective observational study of patients included in this program was to provide data recorded in real-life settings. METHODS: We analysed 89 patients enrolled in Ro-PAP, CA 184-427 (54 men and 35 women) aged between 29 and 89 years. The patients received ipilimumab 3mg/kg, administered with short 30-min i.v. infusion every 3 weeks, having a total of 4 doses. Patients were assessed for tumor response, overall survival (OS) and progression-free survival (PFS), and were monitored for adverse events (AE). RESULTS: At 12 weeks after the completion of therapy, the complete and partial response rates were 6.74% each, stable disease 15.73%, with the best overall response rate 13.48% and disease control rate 29.21%. Median OS was 189.00 days (95% CI 69.50-308.49) and median PFS 124.00 days (95% CI 85.05-162.94). The level of patient functionality at the beginning of ipilimumab treatment showed to be an important predictor of outcome, as patients with ECOG performance status (PS) (0) before therapy with ipilimumab had a higher OS compared with those with impaired functionality. CONCLUSIONS: The use of ipilimumab in daily clinical practice demonstrated to be effective and safe, consistent with data coming from randomized clinical trials or other observational studies.

Perception of disease, dyadic coping, and the quality of life of oncology patients in the active treatment phase and their life partners: an approach based on the actor-partner interdependence model.

Objective: The aim of this study based on the Systemic Transactional Model was to examine the relationship between dyadic coping and (1) disease perception and (2) quality of life of a sample of cancer patients and their life partners. Method: This cross-sectional study included 138 oncological dyads. The following questionnaires were used: Stress Appraisal Measure, Dyadic Coping Inventory, and European Organisation for Research and Treatment of Cancer QLQ-C30. Data collected was analysed by applying the actor-partner interdependence model. Results: The perception of the disease as a threat as well as its centrality significantly negatively influences the positive forms of dyadic coping whilst the perception of the disease as a challenge has a significant positive influence on them. Dyadic coping does not influence symptoms but has significant influences on global health/quality of life. Conclusion: This study has highlighted new information regarding how couples cope with cancer. The results encourage the inclusion of the perception of the disease and dyadic coping in interventions that aim to improve the quality of life of cancer patients and their life partners.

Pregnancy in a Young Patient with Metastatic HER2-Positive Breast Cancer-Between Fear of Recurrence and Desire to Procreate.

Breast cancer is the most frequent neoplasm among women and the second leading cause of death by cancer. It is the most frequent cancer diagnosed during pregnancy. Pregnancy-associated breast cancer is defined as breast cancer that is diagnosed during pregnancy and/or in the postpartum period. Data about young women with metastatic HER2-positive cancer who desire a pregnancy are scarce. The medical attitude in these clinical situations is difficult and nonstandardized. We present the case of a 31-year-old premenopausal woman diagnosed in December 2016 with a stage IV Luminal HER2-positive metastatic breast cancer (pT2 N0 M1 hep). The patient was initially treated by surgery in a conservative manner. Postoperatively, the presence of liver metastases was found by CT investigation. Consequently, line I treatment (docetaxel l75 mg/m² iv; trastuzumab 600 mg/5 mL sq) and ovarian drug suppression (Goserelin 3.6 mg sq at 28 days) was administered. After nine cycles of treatment, the patient's liver metastases had a partial response to the therapy. Despite having a favorable disease evolution and a strong desire to procreate, the patient vehemently refused to continue any oncological treatment. The psychiatric consult highlighted an anxious and depressive reaction for which individual and couple psychotherapy sessions were recommended. After 10 months from the interruption of the oncological treatment, the patient appeared with an evolving pregnancy of 15 weeks. An abdominal ultrasound revealed the presence of multiple liver metastases. Knowing all the possible effects, the patient consciously decided to postpone the proposed second-line treatment. In August 2018, the patient was admitted in the emergency department with malaise, diffuse abdominal pain and hepatic failure. Abdominal ultrasound found a 21-week-old pregnancy which had stopped in evolution, multiple liver metastases and ascites in large quantity. She was transferred to the ICU department where she perished just a few hours later. Conclusions/Discussion: From a psychological standpoint, the patient had an emotional hardship to make the transition from the status of a healthy person to the status of a sick person. Consequently, she entered a process of emotional protection of the positive cognitive distortion type, which favored the decision to abandon treatment and try to complete the pregnancy to the detriment of her own survival. The patient delayed the initiation of oncological treatment in pregnancy until it was too late. The consequence of this delay in treatment led to the death of the mother and fetus. A multidisciplinary team worked to provide this patient with the best medical care and psychological assistance throughout the course of the disease.

Management of HER2-Positive Breast Cancer for a Young Patient with Visceral Crisis-The Adjuvant Role of Lifestyle Changes.

The safety profile and effectiveness of existing anti-HER2-targeted therapies have not been evaluated in patients with breast cancer and visceral crisis. We report the case of a 26-year-old woman who was diagnosed with advanced HER2-positive breast cancer and initially treated with curative intent therapy in a neoadjuvant setting, using Trastuzumab and Pertuzumab in combination with Docetaxel; her cancer recurred two years later, with liver metastases and pulmonary lymphangitic carcinomatosis, causing visceral crisis. Furthermore, the patient's clinical status worsened when she developed respiratory failure, hepatomegaly and a severe hepatocytolysis. Since the patient was free of disease more than six months, we started with Paclitaxel half dose because of the hepatic dysfunction, and we gradually reintroduced Trastuzumab and then Pertuzumab. In the meantime, the patient changed her lifestyle by increasing her consumption of fresh fruits and vegetables and fiber and reducing her intake of processed meat, dairy and sugar. As a result, the patient showed a significant improvement in her respiratory symptoms and liver tests in less than two months. Imaging reevaluation showed partial remission of liver metastases and pulmonary lymphangitic carcinomatosis. She underwent seven months of dual anti-HER2 blockade before relapsing cerebrally. Our results suggest that the sequential combination therapy with Trastuzumab, Pertuzumab and Paclitaxel presented in this study, associated with a healthy lifestyle, may be a good management for recurrent HER2-positive breast cancer with pulmonary visceral crisis and severe liver dysfunction.

Spectrum of BRCA1/2 Mutations in Romanian Breast and Ovarian Cancer Patients.

Background: About 10,000 women are diagnosed with breast cancer and about 2000 women are diagnosed with ovarian cancer each year in Romania. There is an insufficient number of genetic studies in the Romanian population to identify patients at high risk of inherited breast and ovarian cancer. Methods: We evaluated 250 women of Romanian ethnicity with BC and 240 women of Romanian ethnicity with ovarian cancer for the presence of damaging germline mutations in breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively) using Next-Generation Sequencing (NGS) technology. Results: Of the 250 breast cancer patients, 47 carried a disease-predisposing BRCA mutation (30 patients (63.83%) with a BRCA1 mutation and 17 patients (36.17%) with a BRCA2 mutation). Of the 240 ovarian cancer patients, 60 carried a BRCA mutation (43 patients (72%) with a BRCA1 mutation and 17 patients (28%) with a BRCA2 mutation). In the BRCA1 gene, we identified 18 variants (4 in both patient groups (ovarian and breast cancer patients), 1 mutation variant in the BC patient group, and 13 mutation variants in the ovarian cancer patient group). In the BRCA2 gene, we identified 17 variants (1 variant in both ovarian and breast cancer patients, 6 distinct variants in BC patients, and 10 distinct variants in ovarian cancer patients). The prevailing mutation variants identified were c.3607C>T (BRCA1) (18 cases) followed by c.5266dupC (BRCA1) (17 cases) and c.9371A>T (BRCA2) (12 cases). The most prevalent mutation, BRCA1 c.3607C>T, which is less common in the Romanian population, was mainly associated with triple-negative BC and ovarian serous adenocarcinoma. Conclusion: The results of our analysis may help to establish specific variants of BRCA mutations in the Romanian population and identify individuals at high risk of hereditary breast and ovarian cancer syndrome by genetic testing.

Attitudes towards COVID­19 vaccination in patients with cancer: A cross­sectional study of 12 oncology centers.

Patients with cancer are a high-priority population for COVID-19 vaccination, as per guideline recommendations. The present cross-sectional study was performed to assess the perception of patients with cancer from Romania regarding COVID-19 vaccines. The study included 932 patients with solid and hematologic malignancies. This was a multicenter study including 12 oncology centers located in Western and Northwestern Romania. Between December 2021 and January 2022, patients with cancer completed an individual paper questionnaire regarding acceptance of the SARS-CoV-2 vaccination, type of vaccine, side effects and source of information. During the first year of the vaccination campaign in Romania, 58.05% (541/932) of the investigated patients received COVID-19 vaccines. The vaccination rate was highest in the 61-70 year age group (61.22%). The most frequently used vaccine was Pfizer-BioNTech (72%). There was a statistically significant association between the rate of vaccination and the area of residence and level of education (P<0.001), with rural residence and a lower level of education being predictive factors for COVID-19 vaccination hesitancy. Patients living in rural areas used non-medical sources (e.g. mass media, social platforms) as their main source of information (53.40%, 204/382), whereas patients living in urban areas (64.90%, 357/550) used predominantly medical sources (e.g. recommendations from oncologists and general practitioners). The main source of information among non-vaccinated patients was mass media (e.g. television, radio); 72.38% vs. 29.67% among vaccinated patients. For the latter, the primary source of information was the recommendations made by oncologists (59.70%) and general practitioners (56.76%). The most commonly reported side effect was injection site pain (20-33% for the first dose and 5-27% for the second dose). In conclusion, the present study confirmed that patients with cancer may be reluctant to receive a COVID-19 vaccine, mainly due to the fear of its potential side effects. Although there is scientific evidence to support the efficacy and safety of vaccines, the primary source of information for patients may affect vaccine uptake, thus affecting the efforts to stop the pandemic. Furthermore, the present study revealed that non-vaccinated patients preferred mass media as their main source of information, whereas vaccinated patients relied on the recommendations made by oncologists or general practitioners.

Determining factors of renal dysfunction during cisplatin chemotherapy.

Cisplatin remains one of the most active antineoplastic treatments used in oncology, being the most prestigious exponent of the golden age in chemotherapy at the end of the 20th century. This chemotherapeutic drug is used for curative or palliative treatments in testicular, ovarian, head and neck neoplasms, sarcomas and lymphomas. The limiting dose adverse effect of cisplatin is nephrotoxicity. The present study aimed to evaluate the magnitude of the damage to renal function and to identify the risk or protective factors in renal toxicity. The retrospective study was performed using 81 consecutive patients who underwent at least three cycles of cisplatin chemotherapy. The results indicate an average decline in glomerular filtration rate (GFR) of 9 ml/min. Women appear to be less by a decline in renal function (a relative decline of GFR of -5% for women compared to -9% for men). The decline in GFR was found to be proportional to age; overweight (not obese) individuals had the best renal function behavior under cisplatin treatment, while the association of anaemia appears to be a risk factor for renal toxicity. The use of cisplatin in oncology in the last years may have decreased, either by using combination chemotherapy instead of monotherapy, or by its displacement by newly discovered treatments (e.g., immunotherapy in lung cancer). Therefore, it is possible that the profile of patients who are exposed to this drug and the duration of exposure have been modified compared to previous studies. The objectives of the present study were to assess the magnitude of the renal function damage during cisplatin treatment and to identify the risk and the protective factors in term of renal toxicity.

Well-Being, Depression, and Anxiety following Oncoplastic Breast Conserving Surgery versus Modified Radical Mastectomy Followed by Late Breast Reconstruction.

Breast cancer requires complex clinical care. Well-being is an intricate concept, encompassing physical, functional, emotional, and social aspects. BACKGROUND: This study aims to evaluate the relationship between the type of surgery our patients underwent and the timing of the reconstructive surgery with physical, emotional, social, and functional well-being. Furthermore, through our research we tried to identify potential mental health comorbidities in patients with breast cancer, clinical symptoms, and well-being in women with breast cancer, depending on the type of required surgery. METHODS: The study included 69 women diagnosed with breast cancer, in stages I to III, divided in two groups: I-patients with oncoplastic breast-conserving surgery and contralateral correction surgery, for symmetry reasons; II-patients who underwent modified radical mastectomy and late breast reconstruction with contralateral symmetrisation. We evaluated socio-demographic aspects, alongside depression, anxiety, stress (DASS 21), and well-being (FACT-B). Data were statistically processed; statistical significance was set at p < 0.05. RESULTS: Clinical elements of depression, anxiety, and stress were noted in both groups, without statistical significance (p > 0.05). Significant differences were found regarding psycho-emotional (p = 0.035) and functional well-being (p = 0.001), with higher scores for group I. The chi-square test indicated statistically significant differences (at p < 0.01) between the groups, regarding the frequency of scores on items B4 and B9 (FACT-B items, related to feminine aesthetics and desirability), with evidently higher scores in group I than in group II. CONCLUSIONS: The state of well-being, as well as the items related to femininity and sexuality had higher values in the group of women treated by oncoplastic conservative surgery compared to late reconstruction after modified radical mastectomy.

Comparative hematological profiles for dose-dense vs. regular anthracycline-based neoadjuvant chemotherapy in non-metastatic breast cancer.

The aim of the present study was to examine both the feasibility and toxicity of neoadjuvant dose-dense chemotherapy in women with non-metastatic breast cancer. A search within the OncoHelp Association breast cancer database has been performed in order to identify all non-metastatic breast cancer patients who underwent an initial consultation with a medical oncologist between March 2016 and April 2020. The inclusion criteria used were: i) Age, ii) follow-up care obtained at OncoHelp Association, iii) the intent to treat with a neoadjuvant dose-dense anthracycline every two weeks for four cycles (C1-C4) followed by paclitaxel every two weeks for four cycles, with white blood cell growth factor support, and iv) regular anthracycline-based chemotherapy every three weeks for four cycles, followed by paclitaxel every three weeks for four cycles, v) weight, vi) height, vii) Eastern Cooperative Oncology Group (ECOG) performance status, viii) hemoglobin (Hb) level, ix) Platelet count and x) neutrophil count.

The Pattern of Second Primary Tumours in Postmenopausal Women with Prior Breast Cancer in Western Romania: A Retrospective, Single-Institution Study.

With improved survival, more patients with prior breast cancer are at risk of having a second primary cancer diagnosed. The pattern and impact of second primary cancers following breast cancer is important for overall breast cancer therapeutic management. Our study is a first analysis of the trend of second primary tumours over time in terms of incidence, sites with significantly elevated risks and correlation with stage, molecular subtype and therapeutic strategies conducted in Eastern Europe in postmenopausal women with breast cancer. PATIENTS AND METHODS: Our study population included 28 patients with prior breast cancer (BC) and second primary tumours, which were diagnosed and treated in our Institution between 2004 and 2017. The criteria for selection were based on the completeness of the documentation of the first treatment for breast cancer, stage of disease, molecular subtype, the site of origin of the second tumours and the survival data. RESULTS: An increased risk of second primary cancer was associated with the 51-60 years age group (53.6%), with the greater prevalence in patients living in urban environments (82.1%). The use of chemotherapy increased the risk of the occurrence of gynecological second malignancies (75%). Our study is a first analysis of the trend of second primary tumours over time in terms of identifying sites with significantly elevated risks and correlation with therapeutic strategies conducted in Eastern Europe in postmenopausal women with breast cancer. CONCLUSIONS: Our study is a first analysis of the trend of second primary tumours over time in terms of correlation with luminal subtype and stage at diagnosis of primary cancer sites with significantly elevated risks and correlation with therapeutic strategies in postmenopausal women with breast cancer conducted in Eastern Europe. The reported time from primary to second primary malignancy onset, with a significantly higher rate for postmenopausal breast cancer patients, was less than one year (50%). With the advances and wider availability of genetic testing (e.g., gene panels), patients diagnosed with multiple primaries should be increasingly investigated for an underlying cancer predisposition. Postmenopausal women with breast cancer may benefit from increased surveillance and advice to avoid second malignancies.

Carcinomatous-like mastitis due to axillary lymphadenopathy in a case of nasopharyngeal carcinoma: A case report.

Nasopharyngeal carcinoma (NPC) is a rare form of malignancy, accounting for 2% of all cancers of the head and neck in Europe. Axillary lymph node metastases are very rare in these cases. This is a case report of a 40-year-old premenopausal woman diagnosed in May 2015 with T1N2M0 stage III NPC, treated with induction chemotherapy, followed by chemo-radiotherapy. Post-therapeutic computed tomography (CT) scan showed partial response (PR) on the primary tumor and complete response (CR) on the latero-cervical lymph nodes. In 2017, our patient developed left carcinomatous-like mastitis with axillary lymphadenopathy. This raised suspicions of a carcinomatous mastitis. The pathology report with immunohistochemistry (IHC) of the third biopsy highlighted axillary metastasis of a non-keratinizing squamous cell carcinoma (NSCC). There are very few references in the literature regarding axillary metastases from squamous cell carcinoma of the head and neck (HNSCC). As far as we know, this is the first case report of mastitis due to NPC. To conclude, treatment consisted of two surgical excisions of axillary lymphadenopathy associated with local radiotherapy and chemotherapy (neo-adjuvant, adjuvant). The second surgery, performed after radiotherapy, required plastic surgery. A psychiatric evaluation was necessary, revealing a reactive anxiety disorder. This case required multidisciplinary management, where oncology, plastic surgery, pathology and psychiatric specialists collaborated in deciding the therapeutic approach.

Unilateral Orbital Metastasis as the Unique Symptom in the Onset of Breast Cancer in a Postmenopausal Woman: Case Report and Review of the Literature.

The orbit represents an unusual metastases site for patients diagnosed with cancer, however, breast cancer is the main cause of metastases at this level. These orbital metastases were discovered in patients with a history of breast cancer as unique or synchronous lesions. We present a rare case of a unique retroocular metastasis as the first initial symptom of a tubulo-lobular mammary carcinoma in a postmenopausal woman. A 57-year-old patient complains of diplopia, diminishing visual acuity, orbital tenderness, slight exophthalmia and ptosis of the left eyelid, with insidious onset. Clinical examination and subsequent investigations revealed a left breast cancer cT2 cN1 pM1 stage IV. Breast conserving surgery was performed on the left breast. Pathological examination with immunohistochemistry staining established the complete diagnostic: pT2pN3aM1 Stage IV breast cancer, luminal B subtype. After two years from the initial breast cancer diagnosis, the patient was diagnosed by the psychiatrist with a depressive disorder and was treated accordingly. Orbital metastases are usually discovered in known breast cancer patients and they are found in the context of a multi-system end-stage disease. Most reports cite that up to 25% of the total orbital metastases cases are discovered before the diagnosis of the primary tumor, as our case did. MRI is the gold standard for evaluating orbital tumors. The ILC histological subtype metastasizes in the orbitals more frequently than invasive ductal carcinoma. The prognosis of patients with orbital metastases is poor. The median survival after diagnosis of orbital metastases from a breast cancer primary is ranging from 22 to 31 months. Overall survival of our patient was 56 months, longer than the median survival reported in literature. Orbital metastases must be taken into account when patients accuse ophthalmologic symptoms even in the absence of a personal history of cancer. Objective examination of every patient that incriminates these types of symptoms is essential, and breast palpation must be made in every clinical setting. Orbital biopsy is necessary for the confirmation of the diagnosis and for an adequate treatment. Although recommendations for management of orbital metastases are controversial, it appears that multidisciplinary treatment of both metastases and primary cancer improves overall survival.

Updated Overall Survival Analysis From IMpower110: Atezolizumab Versus Platinum-Based Chemotherapy in Treatment-Naive Programmed Death-Ligand 1-Selected NSCLC.

INTRODUCTION: IMpower110 previously revealed significant overall survival (OS) benefit with atezolizumab versus chemotherapy in patients with treatment-naive EGFR- and ALK-negative (wild type [WT]) metastatic NSCLC with high programmed death-ligand 1 (PD-L1) expression (≥50% on tumor cells [TCs] or ≥10% on tumor-infiltrating immune cells [ICs], per SP142 immunohistochemistry assay; p = 0.0106). We present primary OS analyses in lower PD-L1 expression groups and an updated, exploratory analysis in the high PD-L1 expression group. METHODS: This open-label, phase 3 trial randomized patients with PD-L1 expression on greater than or equal to 1% of TC or IC to receive atezolizumab or platinum-based chemotherapy. The primary end point was OS, hierarchically tested in PD-L1 expression WT subgroups: first the high PD-L1 expression subgroup, then the high-or-intermediate PD-L1 expression subgroup (≥5% on TC or IC), and then the any PD-L1 expression subgroup (≥1% on TC or IC). RESULTS: The any PD-L1 expression WT population included 554 patients (excluded 18 EGFR- or ALK-positive patients). With 17 months' additional follow-up, OS improvement in the atezolizumab versus chemotherapy arm was not statistically significant in high-or-intermediate PD-L1 expression WT patients (n = 328; hazard ratio = 0.87, 95% confidence interval: 0.66-1.14, p = 0.3091; median = 19.9 versus 16.1 mo), precluding formal OS testing in any PD-L1 expression WT patients. Exploratory analysis in high PD-L1 expression WT patients (n = 205) revealed maintained OS benefit in the atezolizumab arm (hazard ratio = 0.76, 95% confidence interval: 0.54-1.09; median = 20.2 versus 14.7 mo). Updated safety data continued to favor atezolizumab. CONCLUSIONS: Statistical significance for OS was not revealed in the high-or-intermediate expression WT group, and, as a result, OS in the any PD-L1 expression WT group was not formally tested. No new safety signals were found. This updated analysis of IMpower110 supports using atezolizumab in treatment-naive, metastatic WT NSCLC with high PD-L1 expression.

Postmenopausal Breast Cancer in Women, Clinical and Epidemiological Factors Related to the Molecular Subtype: A Retrospective Cohort Study in a Single Institution for 13 Years. Follow-Up Data.

This study focused on the characteristics of postmenopausal breast cancer in the population of southeastern Europe. This retrospective study explored the clinical, epidemiological, and molecular characteristics of women with postmenopausal breast cancer. MATERIAL AND METHODS: A retrospective cohort study was performed on 721 postmenopausal breast cancer patients selected from the database of our institution. The data collected consisted of age, living environment, location of the breast tumor, stage of the disease, and molecular sub-type. Patient characteristics were collected based on a systematic chart audit from medical records. The data were analyzed using SPSS 20.0 and Pearson analysis. RESULTS: The most frequent age range for breast cancer diagnosis was 51 to 70 years old. Most of the patients (80.7%) came from an urban environment. The vast majority of patients were initially diagnosed in stage II (40.3%) and III (30.3%). The most frequent molecular sub-types were luminal B (39%) and luminal A (35.4%). Almost half of the breast tumors were located in the upper outer quadrant (48.8%). CONCLUSIONS: The results of this study describe the profile of patients in southeastern Europe within our institution diagnosed with postmenopausal breast cancer. In our study, patients were first diagnosed with more advanced stages of breast cancer compared with other European countries.

Endurance of erythrocyte series in chemotherapy.

Hematopoietic bone marrow toxicity is most often the limiting factor for chemotherapy doses. Increasing the intensity of chemotherapy doses (higher doses or more frequent administration) would improve antitumor effects, but the hematological toxicity does not allow these dose increases. This study evaluated the impact of chemotherapies on the parameters belonging to the red blood cell series in the hemogram and aimed to identify some particular evolution profiles. We selected 855 evaluations performed before the administration of chemotherapy belonging to the treatments initiated during the period December 2018-February 2020, containing 5-fluorouracil, cisplatin, docetaxel, epirubicin or pemetrexed. The data of the 644 evaluations related to the cycles 1-4 of chemotherapy were subject to this processing. The average relative loss of hemoglobin is -11% after the first three cycles of treatment, with statistically significant differences in hemoglobin levels in favor of men. There are risk factors associated with higher average losses, such as age <50 years or >65 years (statistically significant), body mass index (BMI) >25, cisplatin treatment (insufficient number of cases to reach statistical significance).

Randomized Phase II Study of Duligotuzumab (MEHD7945A) vs. Cetuximab in Squamous Cell Carcinoma of the Head and Neck (MEHGAN Study).

BACKGROUND: Duligotuzumab, a novel dual-action humanized IgG1 antibody that blocks ligand binding to epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), inhibits signaling from all ligand-dependent HER dimers, and can elicit antibody-dependent cell-mediated cytotoxicity. High tumor-expression of neuregulin 1 (NRG1), a ligand to HER3, may enhance sensitivity to duligotuzumab. METHODS: This multicenter, open-label, randomized phase II study (MEHGAN) evaluated drug efficacy in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) progressive on/after chemotherapy and among patients with NRG1-high tumors. Patients received duligotuzumab (1100 mg IV, q2w) or cetuximab (400 mg/m2 load, 250 mg/m2 IV, q1w) until progression or intolerable toxicity. Tumor samples were assayed for biomarkers [NRG1, ERBB3, and human papillomavirus (HPV) status]. RESULTS: Patients (N = 121) were randomized (duligotuzumab:cetuximab; 59:62), median age 62 years; ECOG 0-2. Both arms (duligotuzumab vs. cetuximab, respectively) showed comparable progression-free survival [4.2 vs. 4.0 months; HR: 1.23 (90% confidence interval (CI): 0.89-1.70)], overall survival [7.2 vs. 8.7 months; HR 1.15 (90% CI: 0.81-1.63)], and objective response rate (12 vs. 14.5%), with no difference between patients with NRG1-high tumors or ERBB3-low tumors. Responses in both arms were confined to HPV-negative patients. Grade ≥3 adverse events (AEs) (duligotuzumab vs. cetuximab, respectively) included infections (22 vs. 11.5%) and GI disorders (17 vs. 7%), contributing to higher rates of serious AEs (41 vs. 29.5%). Metabolic disorders were less frequent with duligotuzumab (10 vs. 16%); any grade rash-related events were less with duligotuzumab (49 vs. 67%). CONCLUSION: While several lines of preclinical evidence had supported the premise that the blockade of HER3 in addition to that of EGFR may improve outcomes for patients with R/M SCCHN overall or specifically in those patients whose tumors express high levels of NRG1, this study provided definitive clinical evidence refuting this hypothesis. Duligotuzumab did not improve patient outcomes in comparison to cetuximab despite frequent expression of NRG1. These data indicate that inhibition of EGFR alone is sufficient to block EGFR-HER3 signaling, suggesting that HER2 plays a minimal role in this disease. Extensive biomarker analyses further show that HPV-negative SCCHN but not HPV-positive SCCHN are most likely to respond to EGFR blockage by cetuximab or duligotuzumab.