5-year Distant Disease-free Survival Rates Research Articles

Postoperative Adjuvant Anastrozole for 10 Rather than 5 Years in Patients with Oestrogen Receptor-Positive Breast Cancer: AERAS, a Randomised Multicentre Open-Label Phase III Trial

Background: Treatment with an aromatase inhibitor for 5 years is the standard treatment for postmenopausal hormone receptor-positive breast cancer. We investigated the effects of extending this treatment to 10 years on the risk of breast cancer recurrence. Methods: This prospective, randomised, multicentre open-label phase III study assessed the effect of extending anastrozole treatment for an additional 5 years in postmenopausal patients with stage I–IIIA hormone receptor-positive breast cancer who were disease-free after treatment with either 5 years of anastrozole alone or 2–3 years of tamoxifen followed by 2–3 years of anastrozole. Patients were allocated randomly (1:1) to continue anastrozole (1 mg/day orally) for an additional 5 years or stop anastrozole, using the central computer at the Comprehensive Support Project for Oncology Research Data Centre. Randomisation was stratified by type of postoperative endocrine therapy, nodal status, prior adjuvant chemotherapy, and facility. The primary endpoint was disease-free survival, including breast cancer recurrence, second primary cancers, and death from any cause. This study is registered with UMIN clinical trials registry, number UMI00818. Findings: We enrolled 1697 patients from 117 facilities between November 2007 and November 2012. Patients were assigned randomly to the continue group (n=849) or the stop group (n=848). Follow-up information was available for 1593 patients (n=787 in the continue group, n=806 in the stop group) as the full analysis set. After a median follow-up of 5·1 years, there were 172 events involving disease recurrence or the occurrence of contralateral breast cancer (75 in the continue group and 97 in the stop group) and 40 deaths (21 in the continue group and 19 in the stop group). The 5-year disease-free survival rates were 91% (95% confidence interval [CI] 89–93) in the continue group and 86% (95% CI 83–88) in the stop group (hazard ratio [HR] for disease-free survival 0·61, 95% CI 0·46–0·82; p<0·0010, two-sided log-rank test). The 5-year overall survival rates were 98% in the continue group and 98% in the stop group (HR 1·13, p=0·7042). The 5-year distant disease-free survival rates were 95% in the continue group and 93% in the stop group (HR 0·68, p=0·0553). Sixty-seven second primary cancers occurred, including 24 in the continue group and 43 in the stop group. Menopausal or bone-related all-grade adverse events were more frequent among patients in the continue group than in the stop group, including higher incidences of hot flashes (111 [14%] vs 81 [10%]), stiff joints (162 [21%] vs 98 [12%]), arthralgia (294 [37%] vs 236 [29%]), and new-onset osteoporosis (370 [47%] vs 355 [44%]). Interpretation: Continuing adjuvant anastrozole for an additional 5 years after 5 years’ initial treatment with anastrozole or tamoxifen is safe and beneficial in postmenopausal patients with hormone receptor-positive breast cancer. Trial Registration: This study is registered with UMIN clinical trials registry, number UMI00818. Funding: The Comprehensive Support Project for Oncology Research of the Public Health Research Foundation Declaration of Interest: None to declare. Ethical Approval: Ethical approval was provided by local ethics committees in each hospital.

Favorable outcomes with de-escalated radiation therapy for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma

AbstractRadiation fields for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have shrunk over time; involved-site radiation therapy (ISRT) has replaced extended-field radiation therapy (EFRT) and involved-field radiation therapy (IFRT), but this has not been validated. The role of systemic therapy is unclear. We reviewed 71 stage I/II NLPHL patients and assessed progression-free survival (PFS), overall survival (OS), locoregional disease-free survival, and distant disease-free survival (DDFS). Median patient age was 39 years, and 61% had stage II disease. Thirty-six (51%) received radiation therapy (RT) only, 6 (8%) received systemic therapy only, and 29 (41%) received both. More patients receiving combined therapy had B symptoms (P = .035) and stage II disease (P = .001). In the RT-only group, 9 (25%) received EFRT, 13 (36%) received IFRT, and 14 (39%) received ISRT; in the combined-modality group, 3 (10%) received EFRT, 7 (24%) received IFRT, and 19 (66%) received ISRT. After a median follow-up of 6.2 years, 15 patients relapsed (13 distant, 2 locoregional). Five-year PFS and OS rates were 86% and 96% and did not differ by treatment. In the RT-only group, follow-up was shorter in the ISRT cohort (2.6 years vs 17.9 years [EFRT] and 8.5 years [IFRT], P < .01), but 5-year PFS did not differ by field size (P = .20). Locoregional control rates were 100% for the RT-only and combined groups, and corresponding 5-year DDFS rates were 93% and 95% (P = .95). Eight patients (11%) experienced a second malignancy (1 within RT field). Six patients died (1 from lymphoma). Use of limited ISRT fields does not appear to increase the risk of locoregional relapse, even when RT is given as single-modality therapy.

Safety of breast-conserving treatment for triple-negative breast cancer

To investigate the effect of risk factors on ipsilateral breast tumor recurrence (IBTR) and distant disease-free survival (DDFS) for patients with triple-negative breast cancer (TNBC) who underwent breast-conserving treatment (BCT). A series of 1 835 patients with primary breast cancer treated with BCT in a single institute between December 1999 and August 2010 were analyzed retrospectively. Totally 1 614 patients, whose characteristics were intact, were analyzed to compare their outcomes with respect to the incidence of IBTR, DDFS and disease-free survival (DFS). All of patients were female. Median age was 47 years (ranging 21 to 92 years, interquartile range 14 years). According to the immunohistochemical results of the patients, 1 614 cases were divided into TNBC group (n=308) and non-TNBC group (n=1 306). The risk factors of relapse after breast-conserving treatment (age at diagnosis, spread to axillary lymph nodes, hormone receptor status, neoadjuvant chemotherapy, and maximal tumor diameter, human epidermal growth factor receptor 2 (HER-2) status, preoperative MRI, the location and extent of the tumor bed defined by CT scans for electron boost planning as part of breast radiotherapy) were studied.χ(2) test was used to compare the distribution of baseline characteristics among subtypes. The probability of survival (or relapse occurrence), and DDFS were calculated using the Kaplan-Meier method. Cumulative incidence functions were used to describe the cumulative hazard from LR, IBTR and DDFS in the presence of competing risks. A total of 1 614 women with primary breast cancer underwent a breast-conserving surgery followed by radiotherapy. The median follow-up period was 77 months (interquartile range 36 months). One hundred and forty patients (8.6%) were lost to follow-up. Overall 5-year IBTR rate was 3.1% (95% CI: 2.2% to 4.0%), 5-year DDFS rate was 95.8% (95% CI: 94.9% to 96.7%) and 5-year DFS rate was 93.8% (95% CI: 92.7% to 94.9%). Lymph nodal involvement (HR=3.03, 95% CI: 1.66 to 5.51, P=0.000) and use of CT information in boost field planning (HR=0.40, 95% CI: 0.20 to 0.80, P=0.010) were associated significantly with IBTR in Cox multivariable analysis. Multivariable analysis showed that TNBC doesn't have a significantly increased risk of IBTR compared with the non-TNBC subtype (HR=0.90, 95% CI: 0.50 to 1.76, P=0.78). TNBC was not an independent risk factor for DDFS or DFS. The multivariable model showed significant effect of nodal status and age at diagnosis on 5-year DDFS rate and 5-year DFS rate. Breast-conserving treatment for TNBC is not associated with increased IBTR compared with non-TNBC subtype. Use of CT information in boost field planning can reduce the risk of ipsilateral breast tumor recurrence for patients undergoing BCT.

Prognostic Value of Bone Marrow Micrometastasis in Patients with Operable Esophageal Squamous Cell Carcinoma: A Long-Term Follow-Up Study

Detection of bone marrow micrometastasis (BMM) has been focused on as a prognostic parameter in various malignant neoplasms recently. This study was designed to evaluate the prognostic significance of BMM detection in patients with operable esophageal squamous cell carcinoma (ESCC) after long-term follow-up. In 61 consecutive patients with ESCC who had undergone radical surgical resection, BMM was detected through reverse transcriptase-polymerase chain reaction (RT-PCR). Correlation between BMM detection and prognosis of the 61 patients was analyzed. BMM was found in 13 patients (21.3%). No significant correlation between BMM detection and tumor, node, metastasis (TNM) stage was found. The median survival time, 5-year overall survival rate, 5-year disease-free survival rate, and 5-year distant disease-free survival rate for cases with positive BMM were 13.0 months, 15.4%, 7.7%, and 34.2%, respectively, compared with that of 66.0 months, 59.7%, 49.1%, and 60.6% for cases with negative BMM (p < 0.05). In multivariate analysis, BMM were found to be an independent factor in the prediction of overall survival (odds ratio [OR] 3.928, p = 0.001), disease-free survival (OR 4.285, p < 0.001), and distant disease-free survival (OR 3.270, p = 0.013). BMM is an independent prognostic factor in the prediction of the subsequent development of metastatic disease and disease outcome for operable ESCC patients, and may be a useful adjunct to conventional tumor staging. Further studies are required to evaluate the value of neoadjuvant or adjuvant systemic therapy in ESCC patients with BMM.

Breast Cancer Subtype and Distant Recurrence after Ipsilateral Breast Tumor Recurrence

There is little information about the impact of breast cancer subtype on prognosis after ipsilateral breast tumor recurrence (IBTR). One hundred eighty-five patients were classified according to breast cancer subtype, as approximated by estrogen receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67, of IBTR, and we evaluated whether breast cancer subtype was associated with distant recurrence after IBTR. There was a significant difference in distant disease-free survival (DDFS) after IBTR according to breast cancer subtype defined by a cutoff of the Ki-67 index of 20% (p=0.0074, log-rank test). The 5-year DDFS rates for patients with luminal A, luminal B, triple-negative, and HER2 types were 86.3, 57.1, 56.6, and 65.9%, respectively. In addition, breast cancer subtype was significantly associated with distant recurrence after IBTR on adjustment for various clinicopathologic factors (p=0.0027, Cox proportional hazards model). Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).

Locoregional Treatment for Breast Carcinoma After Hodgkin's Lymphoma: The Breast Conservation Option

To report clinical and pathologic characteristics and outcome of breast cancer (BC) after irradiation for Hodgkin's lymphoma (HL) in women treated at the Institut Curie, with a special focus on the breast-conserving option. Medical records of 72 women who developed either ductal carcinoma in situ or Stage I-III invasive carcinoma of the breast after HL between 1978 and 2009 were retrospectively reviewed. Median age at HL diagnosis was 23 years (range, 14-53 years). Median total dose received by the mediastinum was 40 Gy, mostly by a mantle-field technique. Breast cancers occurred after a median interval of 21 years (range, 5-40 years). Ductal invasive carcinoma and ductal carcinoma in situ represented, respectively, 51 cases (71%) and 14 cases (19%). Invasive BCs consisted of 47 cT0-2 tumors (82%), 5 cN1-3 tumors (9%), and 20 Grade 3 tumors (35%). Locoregional treatment for BCs consisted of mastectomy with (3) or without (36) radiotherapy in 39 patients and lumpectomy with (30) or without (2) adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast-conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were, respectively, 74.5% (95% confidence interval [CI], 64-88%) and 82% (95% CI, 72-93%) for invasive carcinoma and 100% (95% CI, 100 -100%) and 92% (95% CI, 79-100%) for in situ carcinoma. In patients with invasive tumors, the 5-year distant disease-free survival rate was 79% (95% CI, 69-91%), and 13 patients died of progressive BC. Contralateral BC was diagnosed in 10 patients (14%). Breast-conserving treatment can be an option for BCs that occur after HL, despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position, to protect the underlying heart and lung.

Prognostic Significance of Neutropenia on Day One of Anthracycline-Based Neoadjuvant Chemotherapy in Operable Breast Cancer

Objectives: It is currently unknown whether neutropenia during neoadjuvant chemotherapy for early breast cancer is associated with prognosis. Methods: We retrospectively analyzed 103 breast cancer patients who were treated with neoadjuvant chemotherapy including epirubicin-based chemotherapy followed by docetaxel. The association between neutropenia due to epirubicin-based chemotherapy and distant disease-free survival (DDFS) was assessed. Results: Thirty-one patients (30%) demonstrated neutropenia during the epirubicin-based regimen. Patients without neutropenia showed a significantly (p = 0.004) lower 5-year DDFS rate (64%) than those with neutropenia (97%). In addition, multivariate analysis showed that neutropenia is an independent prognostic factor for DDFS (p = 0.02). Conclusion: Neutropenia occurring in early breast cancer patients during the initial neoadjuvant treatment is strongly associated with a better prognosis.

Prognosis After Ipsilateral Breast Tumor Recurrence and Locoregional Recurrences in Five National Surgical Adjuvant Breast and Bowel Project Node-Positive Adjuvant Breast Cancer Trials

Locoregional failure after breast-conserving surgery is associated with increased risk of distant disease and death. The magnitude of this risk in patients receiving chemotherapy has not been adequately characterized. Our study population included 2,669 women randomly assigned onto five National Surgical Adjuvant Breast and Bowel Project node-positive protocols (B-15, B-16, B-18, B-22, and B-25), who were treated with lumpectomy, whole-breast irradiation, and adjuvant systemic therapy. Cumulative incidences of ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) were calculated. Kaplan-Meier curves were used to estimate distant-disease-free survival (DDFS) and overall survival (OS) after IBTR or oLRR. Cox models were used to model survival using clinical and pathologic factors jointly with IBTR or oLRR as time-varying predictors. Four hundred twenty-four patients (15.9%) experienced locoregional failure; 259 (9.7%) experienced IBTR, and 165 (6.2%) experienced oLRR. The 10-year cumulative incidence of IBTR and oLRR was 8.7% and 6.0%, respectively. Most locoregional failures occurred within 5 years (62.2% for IBTR and 80.6% for oLRR). Age, tumor size, and estrogen receptor status were significantly associated with IBTR. Nodal status and estrogen and progesterone receptor status were significantly associated with oLRR. The 5-year DDFS rates after IBTR and oLRR were 51.4% and 18.8%, respectively. The 5-year OS rates after IBTR and oLRR were 59.9% and 24.1%, respectively. Hazard ratios for mortality associated with IBTR and oLRR were 2.58 (95% CI, 2.11 to 3.15) and 5.85 (95% CI, 4.80 to 7.13), respectively. Node-positive breast cancer patients who developed IBTR or oLRR had significantly poorer prognoses than patients who did not experience these events.

Repeat Lumpectomy for Patients with Ipsilateral Breast Tumor Recurrence after Breast-Conserving Surgery

In this study, we assessed the appropriateness of conducting repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) based on the characteristics of recurrence after primary breast conserving surgery (BCS). Of 41 patients who had developed IBTR from October 1986 to June 2000 at our institute, 11 underwent mastectomy of the remaining breast and 30 underwent repeat lumpectomy. The 5-year overall survival rate at a median follow-up of 43 months after salvage surgery was 90.9% for the mastectomy group and 90.0% for the lumpectomy group. The 5-year distant disease-free survival rate was 70.1% for the mastectomy group and 83.0% for the lumpectomy group. The survival rates were remarkably high in both treatment groups, with no significant difference between them. IBTRs in the majority of our patients were small lesions less than 1 cm in diameter. They did not feature lymphatic invasion and had low histological grade. Compared with that of primary lesions, the malignancy of recurrent tumors was not increased in many patients. In contrast to these preferable features, 9 of 30 patients who underwent repeat lumpectomy developed second local relapse within 3 years after salvage operation. Young age (≤35 years), positive family history and omission of adjuvant systemic therapy were found to exhibit trends as a discriminate for further local recurrences. In view of the relatively good prognosis of IBTRs and excellent results of repeat lumpectomy, we consider this method a treatment option that deserves serious consideration if we can select the patients who will not likely develop second local relapse.

Omission of histologic grading from clinical decision making may result in overuse of adjuvant therapies in breast cancer: results from a nationwide study.

To investigate the influence of routinely performed histologic grading on breast cancer outcome prediction and patient selection for adjuvant therapy. The analysis is based on a cohort of 2,842 women diagnosed with breast cancer and comprising 91% of all breast cancers diagnosed in five defined geographical regions in Finland in 1991 through 1992. Data on clinicopathologic factors and follow-up were collected from hospital case records and national registries. Histologic grade assessed at diagnosis and other clinicopathologic data were available for 1,554 operable unilateral invasive carcinomas. The relative value of grade with respect to competing prognostic factors was estimated with the Cox proportional hazards model and logistic regression. Interactions and nonlinearity of factors were accounted for by using an artificial neural network. Histologic grade was correlated strongly with survival in the entire series and in all subgroups studied. Women with well-differentiated node-negative cancer had a 97% 5-year distant disease-free survival rate as compared with 78% for women with poorly differentiated cancer. Grade was an independent prognostic factor in multivariate models and increased the predictive accuracy of a neural network model. Inclusion of grade data in a Cox multivariate model based on tumor size and hormone receptor status in node-negative cancer increased the proportion of patients with 5% or less risk for distant recurrence at 5 years from 15% to 54%. Even when assessed by pathologists who have no special training in breast cancer pathology, histologic grade has substantial and independent prognostic value in breast cancer. Omission of grading from clinical decision making may result in considerable overuse of adjuvant therapies.