RESUMEN

BACKGROUND: As the pulmonary system and cardiovascular system are intimately linked, patients with chronic obstructive pulmonary disease (COPD) and asthma have high risk for developing cardiovascular diseases (CVDs) and altered central hemodynamic. OBJECTIVE: We aim to assess the central aortic blood pressure (CABP) indices, pulse wave velocity (PWV) and other indicators of arterial stiffness in Indian patients with COPD and bronchial asthma. METHODS: This is a single-center, cross-sectional study conducted in outpatients diagnosed with either chronic stable phase of COPD or bronchial asthma. CABP indices, vascular age, arterial stiffness and central hemodynamics were measured in patients. RESULTS: Of 193 patients with obstructive airway disease who were enrolled, (n = 81 had COPD and n = 112 had partially-controlled bronchial asthma) the proportion of male patients was higher in both groups. The PWV, augmentation index (AI) and vascular age (VA) were significantly higher in patients with COPD compared to those with bronchial asthma (all, p < 0.05). CONCLUSION: The study showed that PWV, AI and VA were higher in patients with stable COPD without any cardiac comorbidities compared to bronchial asthma.

Asunto(s)

Asma , Enfermedad Pulmonar Obstructiva Crónica , Análisis de la Onda del Pulso , Rigidez Vascular , Humanos , Masculino , Rigidez Vascular/fisiología , Femenino , Persona de Mediana Edad , Asma/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Estudios Transversales , Adulto , Presión Arterial/fisiología , Aorta/fisiopatología , Presión Sanguínea/fisiología

RESUMEN

BACKGROUND: Treatment of drug-resistant tuberculosis with bedaquiline-pretomanid-linezolid regimen has demonstrated good treatment efficacy. Given linezolid's toxicity profile, prudence suggests reconsidering its dose and duration. We determined the effectiveness and safety of structured dose reduction of linezolid with bedaquiline and pretomanid in adults with pre-extensively drug-resistant (pre-XDR) or treatment-intolerant/nonresponsive multidrug-resistant (MDRTI/NR) pulmonary tuberculosis. METHOD: Adults with pre-XDR or MDRTI/NR pulmonary tuberculosis were enrolled in a multicenter, parallel-group, randomized clinical trial in India. Patients were randomized to 26 weeks of bedaquiline, pretomanid, and daily linezolid, at 600 mg for 26 weeks (arm 1); 600 mg for 9 weeks followed by 300 mg for 17 weeks (arm 2); or 600 mg for 13 weeks followed by 300 mg for 13 weeks (arm 3). Study end points included sustained cure, bacteriological failure, toxicity, and death. RESULTS: Of 403 patients enrolled, 255 (63%) were <30 years old, 273 (68%) had prior tuberculosis episodes, and 238 (59%) were malnourished. At the end of treatment, after excluding those with negative baseline cultures, cure was seen in 120 (93%), 117 (94%), and 115 (93%) in arms 1, 2, and 3 respectively. Myelosuppression seen in 85 patients each in arms 1 and 2 and 77 patients in arm 3, not significantly different. Peripheral neuropathy was noticed in 66 patients (30, 17, and 19 in arms 1, 2, and 3) at 10-26 weeks (P = .02). The linezolid dose was reduced because of toxicity in 13, 2, and 4 patients in arms 1, 2, and 3, respectively. CONCLUSIONS: In adults with pre-XDR or MDRTI/NR pulmonary tuberculosis, structured linezolid dose reduction to 300 mg/d is as effective as the standard 600-mg dose but with fewer cases of peripheral neuropathy when given with bedaquiline and pretomanid. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2021/03/032189).

RESUMEN

Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary autosomal dominant condition characterized by benign cutaneous lesions, lung cysts, and increased risk of spontaneous pneumothorax and renal cancer. We report a case of a young Indian boy with bilateral pneumothorax as the first symptom of BHDS. Detailed history examination and investigation showed multiple facial lesions; his computerized tomography was suggestive of renal angiomyolipoma, hepatic angiomyolipoma, pulmonary cyst with pneumothorax, and small bilateral subependymal soft tissue density lesion with calcification in the brain, all of which were collectively suggestive of BHDS. Identification of the above commonly presented clinical features as a syndrome is important for even a primary care physician so as to ensure the timely management and if required referral to a higher center.

RESUMEN

ABSTRACT: Sclerosing epithelioid fibrosarcoma (SEF) and low-grade fibromyxoid sarcoma (LGFMS) constitute a morphological continuum with certain overlapping histopathological features and MUC 4 immunopositivity. SEF is characterized by EWSR1 gene rearrangement, is relatively more aggressive and shows a limited response to chemotherapy. Lately, a subset of tumors with morphological features of SEF, but lacking MUC4 immunostaining and EWSR1 gene rearrangement have been observed. We report the first case of YAP1∷KMT2A-positive sarcoma from the Indian subcontinent along with a review of similar tumors reported previously. A case of 31-year-old male presented with a 3 cm painful lump in the right suboccipital region. Histopathological examination of the excised specimen revealed a cellular tumor composed of atypical spindle and epithelioid cells, exhibiting moderate nuclear pleomorphism, arranged in cords, embedded in a dense collagenous/hyalinized stroma. By immunohistochemistry, the tumor cells were diffusely positive for cyclin D1 and negative for MUC4, desmin, myogenin, ß-catenin, STAT6, myoD1, SMA, and S100P. By fluorescence in-situ hybridization, EWSR1 gene rearrangement was negative. Next-generation sequencing (NGS) revealed YAP1exon5∷KMT2Aexon4 fusion. Given a positive resection margin, he underwent a revision surgery involving wide local excision of the lesion including the outer table of the occipital bone followed by image-guided radiation therapy. Over 2 years of his follow-up, the patient is alive with no evidence of recurrence. Thus, YAP1∷KMT2A positive sarcomas have distinct molecular and overlapping histopathological features with SEF, with relatively less aggressive disease course. Documentation of additional similar tumors with long-term follow-up is required.

RESUMEN

BACKGROUND: Pericardial effusion is the accumulation of fluid in the pericardial cavity. In nations with high tuberculosis (TB) load, TB is the most common cause of pericardial effusion. 1-2% of patients with pulmonary TB develop Pericardial TB worldwide. Multi-drug-resistant (MDR) TB, including extrapulmonary TB (EPTB) cases, are rising in number. Adenosine Deaminase (ADA) is an enzyme in lymphocytes and myeloid cells, which has certain immune functions in the body. ADA levels are increased in inflammatory conditions, like pleural, pericardial, or joint effusions, of bacterial etiology, granulomatous conditions, neoplasms, and autoimmune pathologies. TB is the only lymphocytosis involving disease with increased ADA levels. MDR EPTB is rare, but cases are on the rise, and tuberculous pericardial effusion is one such example. Hence, it is important to know the percentage of cases detected by a culture that can be identified by cartridge-based nucleic acid amplification test (CBNAAT), their resistance patterns, and to identify potential markers like ADA, which can help in early identification of cases. The objectives of this study were to identify the Mycobacterium tuberculosis (MTB) bacilli in culture, and correlate them with cartridge-based nucleic acid amplification test (CBNAAT) results and their drug-resistance, in the Pericardial tubercular effusion, and to find if Adenosine Deaminase (ADA) levels can be used as a predictor of the presence of MTB in pericardial fluid. METHODOLOGY: We enrolled 52 patients with moderate to large tuberculous pericardial effusion, based on pericardial fluid analysis, CBNAAT, and culture methods, between January 2021 and December 2021. RESULTS: The mean age of the patients was 41.85 + 17.88 years, with a median of 38 years. Males made up 57.7% of the total patients. MTB was detected in 16 (30.8%) patients in the CBNAAT evaluations. 14 (87.5%) of the CBNAAT-positive TB patients were sensitive to Rifampicin, whereas the remaining 2 (12.5%) were resistant to Rifampicin on CBNAAT. MTB was found to be growing in 8 (15.38%) drug sensitivity test cultures. Out of these 8, 6 were sensitive to first-line drugs, whereas 2 were resistant to both Isoniazid and Rifampicin. The presence of cough was found to have a significant difference between CBNAAT-detected MTB positive and negative patients (p = 0.020), whereas an insignificant difference was found for the presence of hypertension, diabetes mellitus, obesity, dyspnea, or fever. There was also an insignificant difference between the number of patients positive for the Tuberculin skin test, between the two groups. ADA was significantly higher in the MTB-detected CBNAAT group (85.91 + 37.60U/L vs 39.78 + 24.31U/L, p = 0.005), whereas the total leukocyte count, lymphocytes, neutrophils, random blood sugar levels, and serum protein levels had no significant difference. The area under the Receiver Operator Curve (CBNAAT positive: dependent variable; ADA: test result variable) was 0.854 (null hypothesis rejected), with a standard error of 0.078. CONCLUSIONS: Culture is the gold standard method to diagnose tuberculosis. Detection of MTB on pericardial fluid culture is very uncommon, though in our study, culture came out positive in 16% of patients, and 4% were resistant to rifampicin and isoniazid. Higher ADA levels in pericardial fluid are an indicator of tuberculous pericardial effusion.

Asunto(s)

Adenosina Desaminasa , Mycobacterium tuberculosis , Técnicas de Amplificación de Ácido Nucleico , Derrame Pericárdico , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Adenosina Desaminasa/análisis , Adenosina Desaminasa/metabolismo , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Masculino , Adulto , Femenino , Derrame Pericárdico/microbiología , Persona de Mediana Edad , Líquido Pericárdico , Adulto Joven , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Pericarditis Tuberculosa/diagnóstico

RESUMEN

BACKGROUND AND OBJECTIVE: Tobacco smoking is an established risk factor for chronic obstructive pulmonary disease (COPD). Current evidence suggests that non-tobacco-related risk factors vary geographically and are less understood than smoking. This study aims to compare the risk factors, symptoms, and clinical features of smoking (S-COPD) and non-smoking (NS-COPD) in a COPD population. MATERIALS AND METHODS: In this retrospective cross-sectional study, 489 COPD patients were screened. Data on socio-demographics, smoking and medical history, other risk factors, symptoms, and clinical characteristics including COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) Dyspnea Scale were examined. RESULTS: Of the total selected 416 COPD patients, 35.34% were NS-COPD while 64.66% were S-COPD. S-COPD was predominant in males, whereas NS-COPD was predominant in females (P < 0.0001). In NS-COPD, biomass fuel exposure was a major risk factor (P < 0.0001), and 61% of subjects had a biomass fuel exposure index of >60. In bivariate and multivariate analyses, no risk factors were correlated with forced expiratory volume in 1 second (FEV1)% predicted, while among clinical features, duration of illness (P = 0.001) was correlated with lower values of FEV1 in the multivariate table of S-COPD. In the multivariate analysis, biomass fuel exposure (P = 0.039) and CAT score (P < 0.0001) were correlated with FEV1(%) in NS-COPD. CONCLUSION: Biomass fuel exposure is a substantial risk factor for NS-COPD and was correlated with FEV1(%) predicted. In addition, the CAT score correlated with disease severity in patients with NS-COPD. The development of COPD in non-smokers is being recognized as a separate phenotype and it should be managed according to risk factors.

RESUMEN

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking. Each guideline is accompanied by the level of evidence (LoE), grade of recommendation (GoR) and percentage of consensus reached at the consensus conferences. Updated diagnostic and treatment algorithms are also provided. The guidelines represent the best management options for patients living with ABC globally, assuming accessibility to all available therapies. Their adaptation (i.e. resource-stratified guidelines) is often needed in settings where access to care is limited.

Asunto(s)

Neoplasias de la Mama , Cuidados Paliativos , Humanos , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Femenino , Cuidados Paliativos/normas , Consenso , Guías de Práctica Clínica como Asunto

Asunto(s)

Supervivientes de Cáncer , Neoplasias , Humanos , Femenino , Embarazo , Neoplasias/terapia , Salud Materna , Investigación Biomédica , Lagunas en las Evidencias

RESUMEN

Muscular tuberculosis as a primary focal lesion in an immunocompetent individual without any underlying bone involvement is a rare finding. The authors present a case of a young female in her 30s who presented with complaints of recurrent discharging sinus in the posteromedial aspect of the proximal right thigh for eight months. The patient was treated by surgical debridement followed by antitubercular therapy (ATT) and has shown full recovery during the post-eight-month treatment period. Such a presentation of primary tubercular pyomyositis imposes a diagnostic as well as a therapeutic challenge.

Asunto(s)

Antieméticos , Antineoplásicos , Náusea , Olanzapina , Vómitos , Humanos , Olanzapina/efectos adversos , Olanzapina/uso terapéutico , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & control , Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico

RESUMEN

PURPOSE: Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India. PATIENTS AND METHODS: This study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018. RESULTS: There were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT-151, 77-local treatment, 9-tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars. CONCLUSION: The novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.

Asunto(s)

Administración Metronómica , Fibromatosis Agresiva , Metotrexato , Centros de Atención Terciaria , Humanos , Masculino , Femenino , Adulto , Fibromatosis Agresiva/tratamiento farmacológico , Fibromatosis Agresiva/mortalidad , Fibromatosis Agresiva/economía , India , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven , Persona de Mediana Edad , Adolescente , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Metotrexato/economía , Nivel de Atención , Niño , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Tamoxifeno/administración & dosificación , Tamoxifeno/economía , Tamoxifeno/uso terapéutico , Estudios Retrospectivos

Asunto(s)

Esteroides , Tuberculosis , Humanos , Esteroides/uso terapéutico , Tuberculosis/tratamiento farmacológico

Asunto(s)

Sistemas Electrónicos de Liberación de Nicotina , Humanos , Cese del Hábito de Fumar/métodos , Vapeo/efectos adversos

RESUMEN

OPINION STATEMENT: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life.

Asunto(s)

Neoplasias de la Mama , Calidad de Vida , Femenino , Humanos , Ovario/patología , Tamoxifeno/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/etiología , Neoplasias de la Mama/patología , Premenopausia , Quimioterapia Adyuvante/efectos adversos , Antineoplásicos Hormonales/uso terapéutico

RESUMEN

ABSTRACT: The incidence of breast cancer is increasing rapidly in urban India due to the changing lifestyle and exposure to risk factors. Diagnosis at an advanced stage and in younger women are the most concerning issues of breast cancer in India. Lack of awareness and social taboos related to cancer diagnosis make women feel hesitant to seek timely medical advice. As almost half of women develop breast cancer at an age younger than 50 years, breast cancer diagnosis poses a huge financial burden on the household and impacts the entire family. Moreover, inaccessibility, unaffordability, and high out-of-pocket expenditure make this situation grimmer. Women find it difficult to get quality cancer care closer to their homes and end up traveling long distances for seeking treatment. Significant differences in the cancer epidemiology compared to the west make the adoption of western breast cancer management guidelines challenging for Indian women. In this article, we intend to provide a comprehensive review of the management of breast cancer from diagnosis to treatment for both early and advanced stages from the perspective of low-middle-income countries. Starting with a brief introduction to epidemiology and guidelines for diagnostic modalities (imaging and pathology), treatment has been discussed for early breast cancer (EBC), locally advanced, and MBC. In-depth information on loco-regional and systemic therapy has been provided focusing on standard treatment protocols as well as scenarios where treatment can be de-escalated or escalated.

Asunto(s)

Neoplasias de la Mama , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Emociones , Composición Familiar , India/epidemiología

RESUMEN

Pulmonary sequestration and cystic pulmonary adenomatoid malformation are rare congenital cystic disorders of the lungs. The presence of both the diseases in the same individual is therefore very uncommon. Pulmonary sequestration is a nonfunctional pulmonary tissue mass that derives its blood supply from systemic blood supply other than pulmonary circulation. Congenital cystic pulmonary adenomatoid malformation represents a mass consisting of abnormal bronchiolar air spaces and a deficiency of functional alveoli. This is the case report of a 9-year-old girl with intermittent fever, left-sided chest pain, and cough for the past 15 days along with recurrent coughs since childhood suggestive of hybrid pulmonary sequestration, congenital cystic adenomatoid malformation, and dextrocardia.

RESUMEN

PURPOSE: The treatment outcomes of adolescent and young adult (AYA) cancers have improved with advanced oncology care. Hence, fertility preservation (FP) and post-therapy pregnancies (PTPs) become vital issues. MATERIALS AND METHODS: An online survey link with 17 questions regarding oncofertility and PTPs was circulated among oncologists to assess the knowledge, understand the oncofertility care patterns, and seek suggestions to improve oncofertility services. RESULTS: The median age of 179 respondents, predominantly medical oncologists (68.7%), was 37 years (IQR, 10; range, 29-74), working in academic centers (39%) having a median experience of 4 years (IQR, 4; range, 1-42); 23 (12.8%) had dedicated AYA cancer units. Although a quarter (19%-24%) of respondents discussed fertility issues in >90% of AYA patients with cancer, only a tenth (8%-11%) refer >90% for FP, with significantly higher (P < .05) discussions and referrals in males and by more experienced oncologists (P < .05). Forty-six (25.6%) were not well versed with international guidelines for FP. Most (122, 68.1%) oncologists knew about the referral path for semen cryopreservation; however, only 46% were knowledgeable about additional complex procedures. One hundred and ten (61.5%) oncologists never or rarely altered the systemic treatment for FP. Prominent barriers to FP were ignorance, lack of collaboration, and fear of delaying cancer treatment. Lead thrust areas identified to improve FP practices are education, and enhanced and affordable access to FP facilities. Seventy-four (41.3%) respondents knew about international guidelines for PTPs; however, only half (20%) of them often monitored fertility outcomes in survivors. Oncologists have conflicting opinions and uncertainties regarding pregnancy safety, assisted reproductive techniques, breastfeeding, and pregnancy outcomes among survivors. CONCLUSION: Oncologists are uncertain about the guidelines, FP practices, referral pathways, and PTPs. Multipronged approaches to improve awareness and provision for affordable oncofertility facilities are needed to enhance AYA cancer outcomes in India, which will be applicable to other low- and middle-income countries too.

Asunto(s)

Preservación de la Fertilidad , Neoplasias , Oncólogos , Masculino , Embarazo , Femenino , Humanos , Adulto Joven , Adolescente , Preservación de la Fertilidad/métodos , Neoplasias/terapia , Fertilidad , Oncología Médica

RESUMEN

BACKGROUND: Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. METHODS: This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13-75 years with an Eastern Cooperative Oncology Group performance status of 0-2, who were receiving doxorubicin-cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0-120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. RESULTS: Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference -1·0% [one-sided 95% CI -100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). INTERPRETATION: Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. FUNDING: Progressive Ladies Welfare Association.

Asunto(s)

Antieméticos , Antineoplásicos , Neoplasias de la Mama , Trastornos de Somnolencia Excesiva , Femenino , Humanos , Masculino , Antieméticos/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Trastornos de Somnolencia Excesiva/inducido químicamente , Trastornos de Somnolencia Excesiva/tratamiento farmacológico , Náusea/inducido químicamente , Náusea/prevención & control , Olanzapina/efectos adversos , Vómitos/inducido químicamente , Vómitos/prevención & control , Vómitos/tratamiento farmacológico

RESUMEN

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Asunto(s)

Neoplasias de la Mama , Genes BRCA1 , Genes BRCA2 , Complicaciones Neoplásicas del Embarazo , Resultado del Embarazo , Adulto , Femenino , Humanos , Embarazo , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Mutación de Línea Germinal , Estudios Retrospectivos , Complicaciones Neoplásicas del Embarazo/genética , Complicaciones Neoplásicas del Embarazo/mortalidad , Internacionalidad