IntroductionThe status of tumor-infiltrating lymphocytes (TILs) has been recently proposed to predict clinical outcome of patients with breast cancer. We therefore studied the prognostic significance of CD8+ TILs and FOXP3+ TILs in residual tumors after neoadjuvant chemotherapy (NAC) and the alterations in these parameters before and after NAC in patients with triple-negative breast cancer (TNBC).MethodsOne hundred thirty-one TNBC patients who received NAC at three institutions were examined. CD8+ TIL and FOXP3+ TIL in residual tumors and biopsy specimens were evaluated by double-staining immunohistochemistry. The CD8+ TIL and FOXP3+ TIL status of the residual tumors was assessed, and the rates of their changes before and after NAC were calculated.ResultsTNBC patients with high CD8+ TIL levels or a high CD8/FOXP3 ratio in residual tumors had significantly better recurrence-free survival (RFS) and breast cancer-specific survival (BCSS) than patients with low values of these parameters. In multivariate analyses, CD8+ TIL exhibited strong prognostic significance for RFS, with a hazard ratio (HR) of 3.09 (95 % confidence interval (CI) 1.537–6.614, P=0.0013). The CD8/FOXP3 ratio was also significantly correlated with RFS (HR=2.07, 95 % CI 1.029–4.436, P=0.0412). TNBC with larger residual tumor size and positive lymph node status, which are known prognostic factors, was independently associated with worse RFS (P=0.0064 and P=0.0015, respectively). High CD8+ TIL levels were a markedly powerful indicator of improved BCSS, with an HR of 3.59 (95 % CI 1.499–9.581, P=0.0036). Nodal status was also associated with BCSS (P=0.0024). TNBC with a high rate of CD8+ TIL changes was associated with significantly better RFS compared with the low group (P=0.011). Higher rates of changes in the CD8/FOXP3 ratio were significantly correlated with both better RFS and BCSS compared with lower rates (P=0.011 and P=0.023, respectively).ConclusionsThis is the first study to demonstrate that high CD8+ TIL and a high CD8/FOXP3 ratio in residual tumors and increment of these parameters following NAC and accurately predict improved prognosis in TNBC patients with non-pathological complete response following NAC. These parameters could serve as a surrogate one for adjuvant treatment in patients with residual disease in the neoadjuvant setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0632-x) contains supplementary material, which is available to authorized users.

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Building on the model of Sanford J. Grossman and Guy Laroque (1990), this paper provides a model of household consumption and portfolio allocation which incorporates the role of housing as both a consumption good and as a component of wealth. The model captures the following features of the household's problem: (a) utility depends, probably nonseparably, on two distinct goods (nondurable consumption and housing); (b) nondurable consumption can be adjusted costlessly, but housing is subject to an adjustment cost; (c) households face housing price risk in the sense that the relative price of housing varies over time; and (d) in addition to the house, the household can invest in a wide variety of financial assets. This single, reasonably tractable, model generates testable implications for portfolio allocation, risk aversion, asset pricing, and the dynamics of nondurable consumption.Because the original Grossman and Laroque model considers a utility function in which the durable good is the sole argument, and thus abstracts completely from nondurable consumption, their analysis cannot address either the potential spillover effects of the adjustment costs of the durable good on the dynamics of nondurable consumption, or the implications for portfolio allocation of housing risk arising from variation in the relative price of housing. In addition to generating implications for issues on which the original Grossman and Laroque model was silent, the housing model delivers a strikingly different message concerning asset pricing. That is, in contrast to the Grossman and Laroque result that the consumption-based Capital Asset Pricing Model (consumption-CAPM) fails, the housing model implies that the consumption-CAPM holds.We assume that the household incurs an adjustment cost when altering the holding of the durable good (or house), although financial assets can be bought and sold costlessly. Consumption of the nondurable good can also be adjusted costlessly. When choosing a new house, the consumer takes into account the fact that the consumption of housing services will be constant at the new level until the subsequent stopping time, when it is again worthwhile to incur the adjustment cost. Thus, the home purchase decision is endogenous and fully rational, but, because of the adjustment cost, infrequent. In this continuous time setting, the household's decision process has a recursive structure; at each instant, the household first decides whether it is optimal to sell the house immediately. On those rare occasions that it is optimal to incur the adjustment cost, the household sells the old house and buys a new one instantaneously. If the household decides that it is not optimal to sell the house immediately, it then determines its optimal holdings of financial assets and optimal level of nondurable consumption conditional on the current housing stock. In essence, because of the adjustment costs associated with the durable good, the current

The anti-tumor immune response was recently reported to play a critical role in the chemotherapeutic sensitivity of breast cancer. Therefore, we investigated the correlation between CD8+ and FOXP3+ tumor-infiltrating lymphocytes and the pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), in conjunction with neoangiogenesis, basal and proliferation markers. CD8+ and FOXP3+ lymphocytes were assessed in biopsy specimens by double-staining immunohistochemistry, in combination with immunostaining of vasohibin-1, CD31, EGFR, CK5/6, and Ki-67. Earlier age, pre-menopausal status, smaller tumor size, and high Ki-67 were significantly associated with pCR, as in high CD8+, high CD8+/FOXP3+ ratio, and low vasohibin-1 positive ratio. Multivariate analysis did reveal that a high CD8+/FOXP3+ ratio was a strong predictor of pCR with an odds ratio of 5.32 (P = 0.005). High Ki-67 was also significantly associated with pCR (P = 0.002). TNBCs with a high CD8+/FOXP3+ ratio and high Ki-67 had the highest pCR rate (70%) following NAC. However, the pCR rate of the patients with low CD8+/FOXP3+ ratio and low Ki-67 was only 5%. The pCR rates of a high CD8+/FOXP3+ ratio and low Ki-67 patients and those with a low CD8+/FOXP3+ ratio and high Ki-67 were 24 and 21%, respectively. TNBCs with a high CD8+/FOXP3+ ratio were more sensitive to anthracycline and taxane-based chemotherapeutic regimens, and the CD8+/FOXP3+ ratio in conjunction with Ki-67 could predict pCR following NAC in TNBC. This predictor may represent a new surrogate for testing the efficacy of investigational agents in the neoadjuvant setting.