Significance of lung biopsy for the definitive diagnosis of lung nodules in breast cancer patients.

The aim of the present study was to evaluate the significance of lung biopsy for the modification of the treatment strategy in breast cancer patients who develop lung nodules during follow-up after breast surgery. Of 53 consecutive patients who underwent lung biopsies in two institutions (Hiroshima University Hospital and Hiroshima Prefectural Hospital, Hiroshima, Japan) between 1997 and 2014, 45 underwent lung surgery and 8 underwent percutaneous or transbronchial tumor biopsy for lung nodules developing after curative surgery for breast cancer. The indications for lung biopsy included lung nodules for which a definitive diagnosis was difficult to achieve, and those for which the treatment strategy depended on the pathological diagnosis. The lung nodules were pathologically diagnosed as primary breast cancer metastases to the lungs in 25 (47%), primary malignant lung tumors in 21 (40%) and benign disease in 7 (13%) patients. Among the 25 metastatic patients confirmed by lung biopsy, phenotype discordance was observed in 6 patients (24%). A total of 3 patients with lung metastasis proven to have estrogen or progesterone receptor upregulation by lung biopsy received endocrine therapy. Univariate analysis revealed that patients with metastatic breast cancer confirmed by lung biopsy were significantly younger and had more locally advanced primary cancers diagnosed via clinical and pathological assessment compared with patients with other diseases. Therefore, mastectomy and axillary lymph node dissection were performed more frequently in the metastasis group compared with the others group. Multivariate analysis revealed that mastectomy (P<0.001) and axillary dissection (P<0.001) were independent factors predicting that the lung nodules would be metastases from breast cancer. Lung biopsy in breast cancer patients who developed lung nodules during the follow-up period after breast cancer surgery was crucial for making a definitive diagnosis and modifying the treatment strategy, which may improve the prognosis of breast cancer patients.

Role of 18F-PET/CT in Predicting Prognosis of Patients With Breast Cancer After Neoadjuvant Chemotherapy.

BACKGROUND: Breast cancer can be assessed preoperatively and postoperatively using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). We prospectively analyzed the maximum baseline standardized uptake value (SUVmax) derived from FDG PET/CT to predict the outcomes after neoadjuvant chemotherapy (NAC) for breast cancer. PATIENTS AND METHODS: We assessed 130 consecutive female patients with primary breast cancer (mean age, 53.9 years) using PET/CT before and after NAC. The SUVmax before (pre-SUVmax) and after (post-SUVmax) NAC and the SUVmax reduction rates (ΔSUVmax) after NAC with sequential anthracyclines and a taxane were assessed to predict the pathologic complete response (pCR) and prognosis. RESULTS: Of the 130 patients, 30 (23.1%) achieved a pCR. The pCR rate of the patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative (TN) breast cancer was 52.8% and 40.0%, respectively. In contrast, only 1.4% of those with estrogen receptor-positive and HER2- cancer achieved a pCR. The post-SUVmax correlated closely with the pCR (area under the curve, 0.700) but not with the pre-SUVmax and ΔSUVmax (area under the curve, 0.414 and 0.589, respectively) in patients with HER2+ and TN breast cancer. The post-SUVmax was associated with the pCR (P = .019), and multivariate analysis selected post-SUVmax as a significant prognostic factor (P = .014). The post-SUVmax correlated significantly with recurrence-free survival and recurrence (P = .026, log-rank test). CONCLUSION: The SUVmax determined after NAC using FDG PET/CT can predict for the pCR and the prognosis of patients with operable HER2+ and TN breast cancer. In the future, additional chemotherapy will be applied according to the post-SUVmax after standard NAC to achieve a pCR or omit surgery.

Prognostic value of Ki67 and p53 in patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer: Validation of the cut-off value of the Ki67 labeling index as a predictive factor.

The aim of this study was to evaluate the significance of the Ki67 labeling index and p53 status as prognostic and predictive indicators of operable estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Among 697 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2013, 308 patients with ER-positive and HER2-negative breast cancer were assessed. The results of the multivariate Cox analysis demonstrated that a high Ki67 labeling index was significantly associated with a short recurrence-free interval (RFI) (p=0.004) and was marginally associated with a worse overall survival (p=0.074). A positive p53 status was not associated with worse outcomes. To validate the cut-off values of the Ki67 labeling index for identifying patients who may benefit from additional chemotherapy, prognostic factors were investigated in breast cancer patients treated postoperatively with endocrine therapy alone. Analysis of receiver operating characteristic curves demonstrated that a Ki67 labeling index cut-off of 20.0% was optimal for predicting recurrence among patients who did not receive adjuvant chemotherapy. The 5-year RFIs for patients with Ki67 <20 and ≥20% were 97.2 and 86.6%, respectively (p=0.0244). A high Ki67 labeling index (≥20%) was significantly associated with large tumors (p<0.01), lymph node metastasis (p=0.0236) and positive p53 status (p<0.001). The univariate analysis demonstrated that Ki67 labeling index ≥20%, lymph node metastasis and progesterone receptor negativity were significant worse prognostic factors for RFI (p=0.0333, 0.0116 and 0.0573, respectively). The Ki67 labeling index was found to be a useful prognostic factor in patients with ER-positive and HER2-negative breast cancer and the cut-off values of the Ki67 labeling index for making a decision regarding adjuvant treatment were validated.

Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor.

Aromatase inhibitors have played a central role in endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer in postmenopausal patients. However, prognostic factors for recurrence following such treatment have not been identified. The current study aimed to validate the prognostic value of endocrine-related progesterone receptor (PgR) status combined with body mass index (BMI). Among 659 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2012, 184 postmenopausal patients with ER-positive (ER+) and human epidermal growth factor receptor type 2-negative (HER2-) breast cancer who were treated with adjuvant aromatase inhibitor therapy were assessed. The patients were assigned to groups based on BMI, according to the WHO cut-off value: ≥25 kg/m2 (high, H) or <25 kg/m2 (low, L). Positive nodal status, negative PgR status, BMI-H and a high Ki-67 labeling index (≥20%) were found to be significantly associated with a short recurrence-free interval (RFI) upon univariate analysis (P=0.048, 0.007, 0.027, and 0.012, respectively). The patients were further grouped based on their combined PgR/BMI status. The RFI was significantly shorter in the PgR- and/or BMI-H group compared with that of the PgR+/BMI-L group (P=0.012). Multivariate analysis revealed PgR- tumors and/or BMI-H and positive nodal status to be independent prognostic factors (P=0.012 and 0.020, respectively). The present findings indicate that PgR/BMI status may serve as a practical tool in the management of ER+ and HER2- breast cancer in patients treated with adjuvant aromatase inhibitors.

[A case of late recurrent breast cancer that responded to radiation therapy and cisplatin plus pemetrexed therapy].

The patient was a 62-year-old woman who had undergone modified radical mastectomy for right breast cancer 19 years before. She was examined at our hospital for cough and hoarseness. After PET-CT and bronchoscopy, she was diagnosed with stage IIIB non-small cell lung cancer. Radiation therapy and cisplatin plus pemetrexed therapy were effective, and she made a recovery from a life-threatening conditon. During observation, a skin nodule was noticed on her right chest wall, and excisional biopsy revealed a skin metastasis from breast cancer. A transbronchial lung biopsy(TBLB)specimen was reexamined, and the lung lesion was shown to be metastasis from breast cancer. By changing to endocrine therapy, the disease has been effectively controlled.