ABSTRACT
PURPOSE: In patients with clinically lymph node-negative (cN0) breast cancer, performing sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) has been preferentially embraced in comparison to before NACT. However, survival outcomes associated with both strategies remain understudied. We aimed to compare the axillary lymphadenectomy (ALND) rate, disease-free survival (DFS), and overall survival (OS), between two strategies. METHODS: We included 310 patients in a retrospective observational study. SNLB was performed before NACT from December 2006 to April 2014 (107 cases) and after NACT from May 2014 to May 2020 (203 patients). An inverse probability of treatment weighting (IPTW) method was applied to homogenize both groups. Hazard ratios (HR) and odd ratios (OR) are reported with 95% confidence intervals (95%CI). RESULTS: The lymphadenectomy rate was 29.9% before NACT and 7.4% after NACT (p < 0.001), with an OR of 5.35 95%CI (2.7-10.4); p = .002. After 4 years of follow-up, SLNB after NACT was associated with lower risk for DFS, HR 0.42 95%CI (0.17-1.06); p = 0.066 and better OS, HR 0.21 CI 95% (0.07-0.67); p = 0.009 than SLNB before NACT. After multivariate analysis, independent adverse prognostic factors for OS included SLNB before NACT, HR 3.095 95%CI (2.323-4.123), clinical nonresponse to NACT, HR 1.702 95% CI (1.012-2.861), and small tumors (cT1) with high proliferation index, HR 1.889 95% (1.195-2.985). CONCLUSION: Performing SLNB before NACT results in more ALND and has no benefit for patient survival. These findings support discontinuing the practice of SLNB before NACT in patients with cN0 breast cancer.
Subject(s)
Axilla , Breast Neoplasms , Lymph Node Excision , Neoadjuvant Therapy , Propensity Score , Sentinel Lymph Node Biopsy , Humans , Sentinel Lymph Node Biopsy/methods , Female , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Neoadjuvant Therapy/methods , Middle Aged , Retrospective Studies , Adult , Aged , Lymph Nodes/pathology , Lymph Nodes/surgery , Neoplasm Staging , Lymphatic Metastasis , Disease-Free Survival , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis , Chemotherapy, Adjuvant , MorbidityABSTRACT
Taxanes are a mainstay of treatment for breast cancer, but resistance often develops followed by metastatic disease and mortality. Aiming to reveal the mechanisms underlying taxane resistance, we used breast cancer patient-derived orthoxenografts (PDX). Mimicking clinical behavior, triple-negative breast tumors (TNBCs) from PDX models were more sensitive to docetaxel than luminal tumors, but they progressively acquired resistance upon continuous drug administration. Mechanistically, we found that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands during the acquisition of drug resistance. In the absence of the drug, the resistant CD49f+ population shrinks and taxane sensitivity is restored. We describe a transcriptional signature of resistance, predictive of recurrent disease after chemotherapy in TNBC. Together, these findings identify a CD49f+ population enriched in tumor-initiating ability and chemoresistance properties and evidence a drug holiday effect on the acquired resistance to docetaxel in triple-negative breast cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Drug Resistance, Neoplasm , Integrin alpha6/metabolism , Taxoids/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Animals , Antineoplastic Agents/pharmacology , Cell Line , Cells, Cultured , Docetaxel , Female , Humans , Integrin alpha6/genetics , Mice , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/transplantation , Taxoids/pharmacology , Triple Negative Breast Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
Bacillary angiomatosis mainly affects the HIV-infected population. Information is limited on the evolution of bacillary angiomatosis during immune restoration following initiation of HAART. We report an unusual case of fatal Bartonella quintana bacillary angiomatosis occurring in an HIV-infected man during the immune restoration phase.
Subject(s)
AIDS-Related Opportunistic Infections/microbiology , Angiomatosis, Bacillary , Bartonella quintana/pathogenicity , Adult , Angiomatosis, Bacillary/diagnosis , Angiomatosis, Bacillary/drug therapy , Angiomatosis, Bacillary/pathology , Antiretroviral Therapy, Highly Active , Bartonella quintana/isolation & purification , CD4 Lymphocyte Count , DNA, Bacterial , Fatal Outcome , HIV Infections/complications , HIV Infections/drug therapy , Humans , Male , Neoplasms, Vascular Tissue/diagnosis , RNA, Ribosomal, 16S/analysisABSTRACT
OBJECTIVE: To establish the frequency, significance and clinical utility of alpha-methylacyl-CoA racemase (AMACR) expression in the hepatobiliary system by performing a wide immunohistochemical screening of AMACR expression. STUDY DESIGN: A total of 204 neoplastic, preneoplastic and normal samples from the hepatobiliary and pancreatic system were immunohistochemically studied on tissue microarrays for AMACR expression and correlated with clinicopathologic parameters. RESULTS: Hepatocellular carcinomas (HCC) showed intense AMACR expression, which was significantly stronger than in nonmalignant tissues and correlated with good differentiation but not with evolution. Weak AMACR expression was observed in cholangiocarcinomas and preneoplastic pancreatic lesions. HCC showed stronger expression than cholangiocarcinomas and ductal pancreatic adenocarcinomas. DISCUSSION: AMACR is strongly expressed in some neoplastic and preneoplastic lesions of the hepatobiIiary system, mainly HCC, and may play a role in malignant transformation and be useful in the differential diagnosis.
