Low number of examined lymph nodes in node-negative breast cancer patients is an adverse prognostic factor.

BACKGROUND: The aim of the study was to determine whether the number of lymph nodes removed at axillary dissection is associated with recurrence and survival in node-negative breast cancer (NNBC) patients. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1606 women with pathologically node-negative T1-T3 invasive breast cancer. Median follow-up was 61 months (range 2-251). Potential prognostic factors assessed included: number of axillary lymph nodes examined, age, menopausal status, tumor size, histological type, tumor grade, estrogen receptor(ER), progesterone receptor (PR) and HER2. RESULTS: At 5 years, relapse-free survival (RFS) rate was 85% and breast cancer-specific survival (BCSS) rate was 94%. In univariate analysis, factors significantly associated with lower RFS and BCSS were: fewer than six lymph nodes examined (RFS, P = 0.01; BCSS, P = 0.007), tumor size >2 cm, grade III, negative ER or PR. Statistically significant factors for lower RFS and BCSS in multivariate analysis were: fewer than six lymph nodes examined [RFS, hazard ratio (HR) 1.36, P = 0.029; BCSS, HR 1.87, P = 0.005], tumor size >2 cm, tumor grade III and negative PR. CONCLUSIONS: Examination of fewer than six lymph nodes is an adverse prognostic factor in NNBC because it could lead to understaging. Six or more nodes need to be examined at axillary dissection to be confident of a node-negative status. This may be useful, in conjunction with other prognostic factors, in the assessment of NNBC patients for adjuvant systemic therapy.     

Geriatric Early-Stage Triple-Negative Breast Cancer Patients in Low-risk Population: Omitting Chemotherapy Based on Nomogram

BackgroundConsidering old age and comorbidities, the actual benefit of chemotherapy in older patients with early triple-negative breast cancer (TNBC) remains uncertain. We aimed to select appropriate patients who could avoid chemotherapy in this population.MethodsA total of 6482 patients more than 65 years old with T1-2N0-1M0 TNBC in 2010-2015 were extracted from SEER program. Multivariate logistic regression was performed to identify independent factors associated with chemotherapy usage. Survival analysis was performed using Kaplan-Meier plots and log-rank tests. Independent prognostic factors were identified by multivariate Cox analysis. A nomogram predicting breast cancer-specific survival (BCSS) and a risk stratification model were constructed.ResultsA total of 3379 (52.13%) patients received chemotherapy while 3103 (47.87%) did not. Age, married status, grade, T-stage, N-stage, radiation and breast-conserving surgery (BCS) were significantly associated with chemotherapy usage (all P < .05). Chemotherapy significantly improved OS (HR = 0.606, P < .001) and BCSS (HR = 0.763, P = .006) in the entire population. A nomogram was built by incorporating independent risk factors (age, T-stage, N-stage, grade and radiation). Based on the score of the nomogram, the risk stratification model demonstrated that chemotherapy improved OS (P < .001) and BCSS (P < .001) of patients in the high-risk group (score >180), but not in the low-risk group (score ≤75).ConclusionChemotherapy is beneficial for geriatric patients with T1-2N0-1M0 TNBC in this study, and the risk stratification model indicates the feasibility of sparing chemotherapy in low-risk subgroup without sacrificing survival, providing clinicians tools to weigh the risk–benefit of chemotherapy and customize the individualized treatment accordingly.     

Additional value and potential use of the 70-gene prognosis signature in node-negative breast cancer in daily clinical practice

BackgroundThe 70-gene prognosis signature has strong prognostic value in node-negative breast cancer, independent of established prognostic factors. It is unclear whether all node-negative patients should receive a signature result. We therefore evaluated its additional prognostic information to a combination of established prognostic guidelines.MethodsWe evaluated 701 patients from three previously described series in whom a signature result was available. Clinical risk was on the basis of Adjuvant! Online (AO), St Gallen guidelines (St G) and Nottingham Prognostic Index (NPI). Overall survival (OS) analyses were carried out in patients treated at the Netherlands Cancer Institute (Amsterdam) who did not receive adjuvant systemic treatment (AST).ResultsOnly 6% (10 of 156) of estrogen receptor (ER)-negative tumours had a good prognosis signature. The signature was not useful for ER-positive tumours and concordant high AO, high St G and/or high NPI clinical risks (N = 139). The 10-year OS estimate for good signature tumours with these characteristics was <80% and AST would therefore be appropriate irrespective of the signature result. In contrast, for patients with a concordant low AO, low St G and/or low NPI risk and in discordant clinical risk patients, the signature identified low-risk patients in whom AST could be safely withheld (10-year OS > 90%).ConclusionThe 70-gene prognosis signature provides additional prognostic information especially in ER-positive lymph node-negative breast cancer patients with a predominant low or discordant clinical risk on the basis of AO, St G and/or NPI.     

Obesity,diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients

BackgroundTo determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy.Patients and methodsWe identified 6342 patients with stage I–III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status.ResultsIn a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 [95% confidence interval (CI) 1.02–1.36], 1.20 (95% CI 1.00–1.42), and 1.21 (95% CI 0.98–1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98–1.31), 1.24 (95% CI 1.04–1.48), and 1.23 (95% CI 1.00–1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98–1.49), 1.39 (95% CI 1.10–1.77), and 1.04 (95% CI 0.75–1.45), respectively.ConclusionsIn patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.     

Prognostic Impact of Extramedullary Infiltration in Pediatric Low-risk Acute Myeloid Leukemia: A Retrospective Single-center Study Over 10 Years

BackgroundThe impact of extramedullary infiltration (EMI) on the clinical outcomes of pediatric patients with acute myeloid leukemia (AML) are controversial.Patients and MethodsA total of 214 pediatric patients with low-risk AML were classified as having EMI (central nervous leukemia [CNSL] and/or myeloid sarcoma [MS]) and not having EMI. Patients with isolated MS before AML diagnosis by bone marrow examination were confirmed with histopathologic examination. For patients diagnosed with AML by bone marrow examination, a thorough physical examination and radiologic imaging were used to confirm MS.ResultsMale gender, a high white blood cell count, the FAB-M5 subtype, t(8;21) and t(1;11) abnormalities, and c-KIT mutations were associated with EMI. The presence of MS was associated with a low complete remission rate (63.6% vs. 79.4%; P = .000) and poor 3-year relapse-free survival (RFS) (62.6% ± 7.5% vs. 87.0% ± 2.8%; P = .000) and 3-year overall survival (73.5% ± 7% vs. 88.8% ± 2.6%; P = .011). Multivariate analysis revealed that MS was a poor prognostic factor for RFS and overall survival. Bone infiltration was an independent risk factor for inferior RFS with MS. Patients with CNSL had a low complete remission rate (58.3% vs. 77.2%; P = .045); however, CNSL did not significantly affect the survival of low-risk patients with AML.ConclusionMS should be considered an independent risk factor to guide stratified treatment.     

Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer--comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial

BACKGROUND: Defining risk categories in breast cancer is of considerable clinical significance. We have developed a novel risk classification algorithm and compared its prognostic utility to the Web-based tool Adjuvant! and to the St Gallen risk classification. PATIENTS AND METHODS: After a median follow-up of 10 years, we retrospectively analyzed 410 consecutive node-negative breast cancer patients who had not received adjuvant systemic therapy. High risk was defined by any of the following criteria: (i) age <35 years, (ii) grade 3, (iii) human epithelial growth factor receptor-2 positivity, (iv) vascular invasion, (v) progesterone receptor negativity, (vi) grade 2 tumors >2 cm. All patients were also characterized using Adjuvant! and the St Gallen 2007 risk categories. We analyzed disease-free survival (DFS) and overall survival (OS). RESULTS: The Node-Negative-Breast Cancer-3 (NNBC-3) algorithm enlarged the low-risk group to 37% as compared with Adjuvant! (17%) and St Gallen (18%), respectively. In multivariate analysis, both Adjuvant! [P = 0.027, hazard ratio (HR) 3.81, 96% confidence interval (CI) 1.16-12.47] and the NNBC-3 risk classification (P = 0.049, HR 1.95, 95% CI 1.00-3.81) significantly predicted OS, but only the NNBC-3 algorithm retained its prognostic significance in multivariate analysis for DFS (P < 0.0005). CONCLUSION: The novel NNBC-3 risk algorithm is the only clinicopathological risk classification algorithm significantly predicting DFS as well as OS.     

Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy

The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed data from 4,683 patients with cancer enrolled in two institutions between 1997 and 2006. We analyzed the correlation between p53 overexpression and relapse, response to adjuvant therapy, breast cancer-specific survival (BCSS), and relapse-free survival (RFS) in patients with primary breast cancer. Overexpression of p53 was noted in 1,091 patients (23.3%). A significant correlation existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, visceral metastasis, and worse BCSS and RFS. Based upon subgroup analyses, combined age (<35, 35–50, and >50 years) and adjuvant therapy (hormone therapy only, chemotherapy only, and hormone therapy following chemotherapy), the greatest reduction of survival based on p53 overexpression was noted in patients 35–50 years of age who received hormone therapy following chemotherapy (P < 0.05). Multivariate analysis showed that p53 overexpression is an independent prognostic factor in patients treated with hormone therapy and chemotherapy (relative risk for BCSS, 2.003; 95% CI, 1.105–3.631; P = 0.022). The p53-overexpressing patients with breast cancer between 35 and 50 years of age who received tamoxifen following chemotherapy had the greatest adverse effect on outcome. Overexpression of p53 is significantly associated with tamoxifen resistance in premenopausal women with breast cancer.     

Tumor Grade and Matrix Metalloproteinase 2 Expression in Stromal Fibroblasts Help to Stratify the High-Risk Group of Patients With Early Breast Cancer Identified on the Basis of St Gallen Recommendations

BackgroundIt is still being discussed if the assessment of basal markers or if adhesion molecules expression contributes additional prognostic information to the classic prognostic factors and hence should be included into standard morphologic reports.Patients and MethodsThe aim of the study was to assess the prognostic significance of: (i) classification recommended by St Gallen experts (ii) tumor grade, expression of (iii) basal markers, (iv) adhesion molecules, and (v) matrix metalloproteinase 2 (MMP-2) in patients with T1-T2 N0M0 chemotherapy-naive ductal breast cancer.ResultsIn 79 patients with tumors characterized by estrogen receptor (ER) and progesterone receptor (PgR) positive, human epidermal growth factor receptor 2 negative (HER2) phenotype and MIB-1 labeling index (MIB-l) LI ≤ 15% (low-risk group) cumulative 17-year breast cancer–specific survival probability was 100% and was significantly higher than in 95 patients from the high-risk group (ER^?/PgR^?/HER2^? or HER2⁺ or MIB-1 LI > 15%) (72.5%). We found that MMP-2 fibroblast expression indicated 2 subgroups with significantly different survival rates in women with grade 3 tumor (88.9% for MMP-2 positivity and 56.0% for negativity). Cox multivariate analysis revealed that both grade 3 combined with stromal fibroblast MMP-2^? and a high-risk group according to St Gallen recommendations are independent negative prognostic factors that influence survival of patients with breast cancer.ConclusionTo the best of our knowledge, we have shown for the first time that MMP-2^? in stromal fibroblasts might indicate poor survivors in the group of patients with grade 3 tumors and that the cumulative effect of both above-mentioned parameters might be helpful in selecting the high-risk individuals from the group of patients with luminal B subtype/HER2⁺/triple negative phenotype identified according to St Gallen recommendations.     

Multifocality and multicentricity in breast cancer and survival outcomes

BackgroundThe clinicopathological characteristics and the prognostic significance of multifocal (MF) and multicentric (MC) breast cancers are not well established.Patients and MethodsMF and MC were defined as more than one lesion in the same quadrant or in separate quadrants, respectively. The Kaplan–Meier product limit was used to calculate recurrence-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS). Cox proportional hazards models were fit to determine independent associations of MF/MC disease with survival outcomes.ResultsOf 3924 patients, 942 (24%) had MF (n = 695) or MC (n = 247) disease. MF/MC disease was associated with higher T stages (T2: 26% versus 21.6%; T3: 7.4% versus 2.3%, P < 0.001), grade 3 disease (44% versus 38.2%, P < 0.001), lymphovascular invasion (26.2% versus 19.3%, P < 0.001), and lymph node metastases (43.1% versus 27.3%, P < 0.001). MC, but not MF, breast cancers were associated with a worse 5-year RFS (90% versus 95%, P = 0.02) and BCSS (95% versus 97%, P = 0.01). Multivariate analysis shows that MF or MC did not have an independent impact on RFS, BCSS, or OS.ConclusionsMF/MC breast cancers were associated with poor prognostic factors, but were not independent predictors of worse survival outcomes. Our findings support the current TNM staging system of using the diameter of the largest lesion to assign T stage.     

EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive,HER2-negative early breast cancer

BackgroundIn early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed.Patients and methodsWe assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan–Meier survival analysis.ResultsAfter 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%–61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years.ConclusionThe EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors.     

Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study

Introduction

The 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).

Methods

One 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.

Results

TNBC 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).

Conclusions

This 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 material

The online version of this article (doi:10.1186/s13058-015-0632-x) contains supplementary material, which is available to authorized users.     

The Association Between Survival and Receipt of Post-mastectomy Radiotherapy According to Age at Diagnosis Among Women With Early Invasive Breast Cancer: A Population-Based Cohort Study

AimsClinical trials of post-mastectomy radiotherapy (PMRT) for early invasive breast cancer (EIBC) have included few older women. This study examined whether the association between overall survival or breast cancer-specific survival (BCSS) and receipt of PMRT for EIBC altered with age.Materials and methodsThe study used patient-level linked cancer registration, routine hospital and radiotherapy data for England and Wales. It included 31 243 women aged ≥50 years diagnosed between 2014 and 2018 with low- (T1-2N0), intermediate- (T3N0/T1-2N1) or high-risk (T1-2N2/T3N1-2) EIBC who received a mastectomy within 12 months from diagnosis. Patterns of survival were analysed using a landmark approach. Associations between overall survival/BCSS and PMRT in each risk group were analysed with flexible parametric survival models, which included patient and tumour factors; whether the association between PMRT and overall survival/BCSS varied by age was assessed using interaction terms.ResultsAmong 4711 women with high-risk EIBC, 86% had PMRT. Five-year overall survival was 70.5% and BCSS was 79.3%. Receipt of PMRT was associated with improved overall survival [adjusted hazard ratio (aHR) 0.75, 95% confidence interval 0.64–0.87] and BCSS (aHR 0.78, 95% confidence interval 0.65–0.95) compared with women who did not have PMRT; associations did not vary by age (overall survival, P-value for interaction term = 0.141; BCSS, P = 0.077). Among 10 814 women with intermediate-risk EIBC, 59% had PMRT; 5-year overall survival was 78.4% and BCSS was 88.0%. No association was found between overall survival (aHR 1.01, 95% confidence interval 0.92–1.11) or BCSS (aHR 1.16, 95% confidence interval 1.01–1.32) and PMRT. There was statistical evidence of a small change in the association with age for overall survival (P = 0.007), although differences in relative survival were minimal, but not for BCSS (P = 0.362).ConclusionsThe association between PMRT and overall survival/BCSS does not appear to be modified by age among women with high- or intermediate-risk EIBC and, thus, treatment recommendations should not be modified on the basis of age alone.     

Controversial Issues Regarding Obligatory Adjuvant Chemotherapy for Stage IIIA Colon Cancer

PurposeTo investigate the survival outcomes of patients with stage IIIA colon cancer. In addition, risk factors that affect the oncologic outcome of stage IIIA colon cancer patients and the role of adjuvant chemotherapy were evaluated.Patients and MethodsData from 326 colon cancer patients with stage IIIA who underwent surgery between January 2000 and December 2016 were retrospectively reviewed. Patients diagnosed with hereditary cancer and those who received preoperative neoadjuvant therapy were excluded.ResultsThe 5-year recurrence-free survival (RFS) rate in stage IIIA colon cancer patients who underwent curative resection was 93.9%. Of the patients with recurrence, the survival rate of those who underwent surgical resection was better than that of patients who received palliative chemotherapy or no treatment (12/13, 92.3% vs. 2/4, 50.0%), respectively; P = .052). Multivariate analysis showed that high serum carcinoembryonic antigen (s-CEA) was an independent and statistically significant prognostic factor for RFS, and ulcerative gross-type disease tended to be a poor prognostic factor. There was no difference in RFS in patients with elevated s-CEA or ulcerative gross-type disease according to receipt of adjuvant chemotherapy.ConclusionPatients with stage IIIA colon cancer had a relatively favorable survival outcome. Even in patients with relapsed disease, long-term survival could be a result if surgical resection is accomplished. High s-CEA concentration is a significant poor prognostic factor for recurrence, and ulcerative gross-type disease tends to be a poor prognostic factor. Postoperative adjuvant chemotherapy may not provide a survival benefit for stage IIIA colon cancer, even in the presence of risk factors. Because of the rarity of this patient group and the low rate of recurrence, large-scale multicenter studies are needed to find and confirm the risk group that would receive a benefit from adjuvant chemotherapy.     

Optimal indications of endocrine therapy alone as adjuvant systemic treatment of breast cancer

We examined the validity of the St Gallen algorithm for Japanese breast cancer patients and sought the optimal indications of endocrine monotherapy as adjuvant systemic treatment. According to the 2005 St Gallen algorithm, endocrine responsiveness (responsive, uncertain, or non-responsive) and recurrence risk (low, intermediate, or high) were assessed in 436 invasive breast cancer patients, who underwent surgery and adjuvant therapy of tamoxifen alone in 1982-1993. Furthermore, intermediate-risk patients were divided into three groups based on lymph node metastasis and number of risk factors as follows: Group A, negative lymph node metastasis and one risk factor; Group B, negative lymph node metastasis and two to five risk factors; and Group C, positive lymph node metastasis. Cumulative 10-year recurrence-free survival (RFS) rates of each type were calculated. Recurrence-free survival was as follows: endocrine responsiveness; responsive: 86.0%, uncertain: 79.5%, non-responsive: 72.4%, risk category; low: 93.3%, intermediate: 84.0%, high: 59.6%, intermediate-risk patients; Group A: 93.5%, Group B: 88.2%, and Group C: 75.0%. In conclusion, patient classification based on St Gallen algorithm appears valid in Japanese breast cancer patients. Endocrine monotherapy may be sufficient as adjuvant treatment in the intermediate-risk patients, in which only one risk factor was present without any metastatic involvement in lymph node.     

Comparison of Autologous Hematopoietic Cell Transplantation and Chemotherapy as Postremission Treatment in Non-M3 Acute Myeloid Leukemia in First Complete Remission

IntroductionA number of randomized trials in patients with AML in CR1 have been conducted and they showed that auto-HCT improves RFS but not OS, compared with chemotherapy. However, because these trials have had compliance problems, the value of auto-HCT still has not been clearly established.Patients and MethodsUsing a database of 2518 adult patients with AML in CR1, we retrospectively analyzed the outcome of auto-HCT and compared it with intensive nonmyeloablative chemotherapy using landmark analyses.ResultsIn 103 auto-HCT recipients, OS and RFS at 3 years from treatment were 65% and 57%, respectively. Multivariate analysis showed that unfavorable risk cytogenetics and entry into CR1 after 2 courses of induction treatment predicted a poor outcome. Because the median time interval between CR1 and auto-HCT was 153 days, landmark analyses at 5 months after CR1 were performed to compare 1290 patients who received chemotherapy alone (median age, 52 years; range, 16-70) with 103 who received auto-HCT (median age, 48 years; range, 16-67). Auto-HCT improves 3-year RFS (58% vs. 37%; P < .001) but not OS compared with chemotherapy alone. Among patients with unfavorable risk cytogenetics or those who required 2 courses to reach CR1, there was no significant difference in RFS between the 2 groups.ConclusionAuto-HCT can be considered as a postremission therapy for AML patients with favorable or intermediate risk cytogenetics who achieve CR1 after a single course of induction treatment.     

Second invasive breast cancers in patients treated with breast-conserving therapy

ObjectiveSecond breast cancers after breast-conserving therapy (BCT) include ipsilateral breast tumor recurrence (IBTR) and metachronous contralateral breast cancer (CBC). Each IBTR is further classified as true recurrence (TR) or new primary tumor (NP). We aim to compare survival outcomes of TR, NP and CBC, and explore the optimal treatments.Methods168,427 patients with primary breast cancer who underwent BCT between 1990 and 2005 were identified in the SEER database. The risks of IBTR and CBC were estimated by annual hazard rate. The breast cancer-specific survival (BCSS) were assessed using multivariable Cox regression analysis.ResultsWith median follow-up of 13 years after BCT, 5413 patients developed an IBTR and 4050 patients had a CBC. The risk of IBTR peaked between 10 and 15 years after BCT, while the risk of CBC distributed evenly. 45.9% of IBTRs were classified as a TR and 54.1% as an NP. The time interval from primary breast cancer to NP was longer than to TR and CBC (P < 0.001). Patients with TR had a poorer BCSS than NP (P = 0.003) and CBC (P = 0.002). There was no difference in BCSS between mastectomy and repeat BCT for treating TR (P = 0.584) or NP (P = 0.243). The BCSS of CBCs treated with BCT was better than mastectomy (P = 0.010). Chemotherapy didn't improve the survival of patients with TR (P = 0.058). However, TRs with grade III or negative hormone receptors benefited from chemotherapy significantly.ConclusionPatients with TR had a poorer BCSS than NP and CBC. Classifying IBTR may provide clinical significance for treatments.     

Efficacy of Immediate Postoperative Instillation of Chemotherapy for Primary Non–Muscle-Invasive Bladder Cancer in Real-World Clinical Practice

BackgroundNon–muscle-invasive bladder cancer (NMIBC) can be treated using transurethral resection (TUR), but high incidence of intravesical recurrence remains a clinical challenge. Single immediate postoperative instillation of chemotherapy (IPIOC) is controversial for NMIBC patients with intermediate recurrence risk. The aim of the present study was to report the efficacy and toxicity of IPIOC, particularly in intermediate-risk NMIBC patients, in the real-world setting.Patients and MethodsWe retrospectively analyzed 363 consecutive patients with primary NMIBC who underwent radical TUR at Kyoto University Hospital between 2007 and 2016.ResultsIn low-risk patients, recurrence-free survival (RFS) was significantly better for IPIOC than non-IPIOC (2-year RFS: 89.3% vs. 59.4%; P = .001). In intermediate-risk patients, IPIOC was associated with significantly longer RFS compared with non-IPIOC (2-year RFS: 85.5% vs. 58.2%; P = .011). IPIOC and bacillus Calmette-Guérin (BCG) were independent predictors for post-TUR recurrence (non-IPIOC vs. IPIOC: hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.14-4.88; P = .02; non-BCG vs. BCG: HR, 2.22; P = .045, 95% CI, 1.02-5.30). In the high-risk group, only BCG was an independent prognostic factor of recurrence in a multivariate Cox proportional hazards model (HR, 2.55; P = .006, 95% CI, 1.32-4.87). There were no significant differences between the BCG-only group and the IPIOC with BCG group in Grade 3 or more local (16 patients [21%] vs. 21 patients [24%]; P = .61) or systemic (3 patients [4%] vs. 6 patients [7%]; P = .40) toxicity rates.ConclusionOur study showed the efficacy of IPIOC for the prevention of intravesical recurrence in primary intermediate-risk NMIBC patients regardless of BCG therapy.     

A combination of HER-2 status and the St. Gallen classification provides useful information on prognosis in lymph node-negative breast carcinoma

BACKGROUND: Adjuvant chemotherapy for patients with lymph node-negative breast carcinoma is being recommended currently based on the St. Gallen classification. The prognostic importance of HER-2 status in patients with lymph node-negative breast carcinoma has been investigated extensively, with contradictory results. The authors investigated the clinical relevance of HER-2 overexpression when combined with the St. Gallen classification in lymph node-negative breast carcinoma. METHODS: The medical records of patients with breast carcinoma negative for lymph node involvement who underwent surgery between January 1995 and December 2000 at the Seoul National University College of Medicine (Seoul, Korea) were reviewed retrospectively. Risk groups based on the St. Gallen classification were categorized as average or minimal risk. The prognostic values of HER-2 in combination with the St. Gallen classification were analyzed with respect to disease-free survival (DFS) rates. RESULTS: A total of 906 patients were eligible for analysis. The overall 7-year DFS rate was 87.5%. The 7-year DFS rates for patients with HER-2-positive and HER-2-negative tumors were, respectively, 77.9% and 91.2% (P = 0.002). The 7-year DFS rates for patients with average and minimal risk group were 85.0% and 97.9%, respectively. The authors found that HER-2 overexpression significantly predicted the risk of disease recurrence (odds ratio = 3.03 [95% confidence interval, 1.63-5.63]). Furthermore, when HER-2 status was combined with the St. Gallen classification, the DFS rate of the HER-2-positive average risk group was 73.3% compared with 88.4% for the HER-2-negative average risk group (P = 0.007). CONCLUSIONS: The combination of HER-2 overexpression and the St. Gallen classification was more useful than either alone to predict the risk of disease recurrence in patients with lymph node-negative breast carcinoma.     

OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer

BackgroundPatients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy.Patients and methodsPatients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%–50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity.ResultsSixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001).ConclusionsInduction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified.Clinical trial registrationClinical trials.gov identifier: NCT02258659.     

Effect of Breast Conservation Therapy vs Mastectomy on Overall Survival and Breast Cancer-Specific Survival Among Men With Stage I-II Breast Cancer: Analysis of SEER, 2000-2018

BackgroundMale breast cancer is a rare malignant tumor, and outcomes of breast conservation therapy (BCT) are currently lacking.MethodThe retrospective, population-based cohort study included 1369 stage I-II (T1–2 N0–1 M0) male breast cancer patients from the SEER database (2000-2018). The patients were grouped in two groups: BCT group and mastectomy group, according to surgical and radiation therapy. Kaplan-Meier method and univariable Cox proportional hazard analysis were used to compare overall survival (OS) and breast cancer-specific survival (BCSS) between two treatment groups. Propensity score matching (PSM) was performed to balance the confounding factors.ResultsOf the 1369 men, 97 (7%) patients received BCT, 1272 (93%) received mastectomy alone. The 5- and 10-year OS rates were 92.3% and 80.7% for BCT group compared with 80.4% and 61.4% for mastectomy group. The 5- and 10-year BCSS rates were 96.5% and 93.9% for patients undergoing BCT, as compared with 93.1% and 84.4% for patients undergoing mastectomy. Compared with mastectomy group, BCT group showed improved OS (hazard ratio [HR], 0.294; 95% CI 0.138-0.623, P = .002) and BCSS (hazard ratio [HR], 0.182; 95% CI 0.040-0.820, P = .027). Of the 791 patients with T1 stage, BCT showed insignificant association with OS (hazard ratio [HR], 0.555; 95% CI 0.207-1.488, P = .242) and BCSS (hazard ratio [HR], 1.217; 95% CI 0.171-8.675, P = .844).ConclusionThe results of this cohort study suggest that BCT is at least equivalent to mastectomy in male breast cancer patients. The underlying mechanism of this association needs further research.