ABSTRACT
BACKGROUND: For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC. PATIENTS AND METHODS: We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs. RESULTS: A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10-40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79-0.92; P < 0.001), and improved OS (HR: 0.87; 95% CI 0.80-0.94; P < 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P < 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (PInt=0.003) and OS (PInt=0.008) with a greater magnitude of positive effect observed for RCB class II than class III. CONCLUSIONS: TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphocytes, Tumor-Infiltrating/immunology , Neoadjuvant Therapy/mortality , Neoplasm, Residual/pathology , Triple Negative Breast Neoplasms/pathology , Aged , CD8-Positive T-Lymphocytes/immunology , Disease Progression , Female , Follow-Up Studies , Humans , Neoplasm, Residual/drug therapy , Neoplasm, Residual/immunology , Prognosis , Receptor, ErbB-2/metabolism , Survival Rate , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/immunologyABSTRACT
A person's intelligence (or IQ) has long been synonymous with cognitive and general abilities to function daily on an effective level. When traumatic brain injury occurs, there is a natural desire to find some measure that identifies the amount of damage that has occurred and whether it is permanent or temporary. Given the popularity of the IQ test, there is a tendency to use this measure as such a yardstick. It is argued that such a global measure is not appropriate. The predominant reason that it is not a wise choice is that IQ test does not tap into many of the critical areas of a person's functioning, such as personality regulation, shorter-term memory, various types of attentional capacity, and the ability to organize and plan effectively. Rather, to truly and accurately reflect a person's neuropsychological strengths and weaknesses requires the use of many different measures, not just a single one such as an IQ score.
Subject(s)
Brain Injuries/psychology , Craniocerebral Trauma , Intelligence Tests , Attention , Brain Injuries/diagnosis , Brain Injuries/etiology , Craniocerebral Trauma/classification , Craniocerebral Trauma/complications , Female , Forensic Psychiatry , Humans , Jurisprudence , Memory, Short-Term , PersonalityABSTRACT
PIP: The American family is becoming stronger because marriage and parenthood are becoming options, not mandates. Previously nearly 95% of Americans were married, a higher percentage than any other country except India. Often people become parents for the wrong reasons, such as parents of the couple wanted grandchildren or the feeling that one must have a baby to have meaning in life. Later marriage is seen as eventually lowering the divorce rate because adults will be mature. Increased use of contraception, and abortion as a last resort, is reducing the number of unplanned, unwanted children who may be abused. Reminders of the motherhood mandate are traditional houses in the suburbs far from jobs. Traditionally commuting times for women have been less than for men, presumably to allow them to spend more time with the children. It is also suggested that schools give realistic courses on parenting and emphasize that having children is not for everyone.^ieng
