Original contributionTumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer☆,☆☆
Introduction
Neoadjuvant chemotherapy (NAC) or preoperative systemic therapy is increasingly considered for patients with operable breast cancer [1], [2]. However, not all patients respond to NAC; some patients go through weeks of NAC without knowing how effective the treatment will be. A pathologic complete response (pCR) has been found to be associated with longer disease-free and overall survival rates [2]. Therefore, we examined factors that were thought to be predictive for response to NAC treatment (pCR), with an eye toward tailoring therapy to a given tumor's characteristics—an approach that is rapidly gaining prominence. Predictive factors for the NAC have been reported by several investigators, and some factors such as tumor grade and biology-based tumor type (based on gene expression profiles) are candidates [3], [4]. However, which type of tumors responds to which treatment is still unclear.
Tumor-infiltrating lymphocytes (TIL) are well-known phenomena, associated with relatively optimistic prognoses [5], as seen in medullary carcinoma in general organs; as an example, gastric medullary carcinoma indicates an excellent prognosis compared with ordinary gastric carcinomas [6]. Similarly, T-cell infiltration is associated with good tumor prognosis in many cancers. In breast cancers, TIL is reportedly a prognostic factor [7]. Interestingly, pCR to NAC is associated with the disappearance of tumor-infiltration Foxp3+ regulatory T cells [8]. In clinical practice, we found that some cases having pCRs to NAC showed marked TIL around cancer cells and/or cancer nests in preoperative needle specimens. We, therefore, considered that TIL might present a predictive marker for breast cancer and examined the pathologic factors predictive for NAC in patients with breast cancer, especially focusing on the correlation of known biology-based tumor type and TIL.
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Subjects
Subjects were patients with breast cancer treated from 2005 to 2010 at the Social Insurance Kurume Daiichi Hospital. Eligibility criteria for this retrospective study were as follows: (1) histologically confirmed invasive carcinoma before NAC on needle biopsy and (2) anthracycline- and/or taxane-based chemotherapy regimen. These patients included 16 cases who achieved pCR and 52 cases who did not respond (non-pCR) to NAC, using an anthracycline- and taxane-based regimen, with a basic protocol
Univariate analysis
The results for univariate analysis were shown in Table 2, and we found 3 factors significantly related to pCR: TIL, HG, and biology-based tumor types (HR−/HER2+). High TIL, high HG, and HR−/HER2+ were significantly associated with pCR (93.7%, P < .0001; 81.3%, P = .0206; 43.7%, P = .014, respectively). Other factors were not significantly associated with responsiveness; notably, HR+/HER2− was 0%, which is considered associated with nonresponsiveness (Table 2).
Multivariate analysis
In Table 3 of the results for
Discussion
Biology-based tumor type has independent predictive and prognostic potential [4]. Darb-Esfahani et al [4] reported that HR+/HER2+–coexpressing carcinomas tend to respond well to NAC and implied favorable prognoses for them, and HR+/HER2− tumors have good prognoses irrespective of pCR. Patients with HR−/HER2− also showed a high pCR rate; however, those who had not achieved pCR had unfavorable prognoses [4]. Other studies showed similar results, although there are still several discrepancies
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This study was supported by funds from Kurume University School of Medicine Alumni Association and Chugai Pharmaceutical Co, Tokyo, Japan.
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Competing interests: None.