Prognostic factors and clinical outcomes of breast cancer patients with disease progression during neoadjuvant systemic therapy.

BACKGROUND: Disease progression during neoadjuvant systemic therapy for breast cancer indicates poor prognosis, while predictors of the clinical outcomes of these patients remain unclear. By comparing the clinical outcomes of patients with different patterns of salvage treatment strategies, we try to evaluate the factors predicting distant failure and explore the favourable treatment for them. METHODS: Patients with disease progression during neoadjuvant systemic therapy for stage I-III breast cancer diagnosed between January 1, 2008 and July 31, 2021 in Fudan University Shanghai Cancer Center were enrolled. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions or the appearance of new breast or nodal lesions. Kaplan-Meier, univariate and multivariate Cox proportional hazard regressions were utilized to compare survival outcomes between different salvage treatment strategies. RESULTS: Among 3775 patients treated with NST, 60 (1.6%) patients encountered disease progression. A significant difference between the outcomes of patients receiving direct surgery and other salvage modalities was found (p = 0.007). Triple-negative breast cancer (p = 0.010) and not receiving direct surgery (p = 0.016) were independently associated with distant disease-free survival on multivariate analysis. CONCLUSIONS: Predictors of distant failure in patients with disease progression include triple-negative breast cancer and not receiving direct surgery. Direct surgery seems to be more favourable than other treatments for patients with disease progression. For inoperable patients, neoadjuvant radiation can increase their operability but not improve their prognosis.

Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy.

The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2-positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT.Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed.At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor-positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR-/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07-15.35; P = 0.039).Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer.

Early Local Recurrence Presents Adverse Effect on Outcomes of Primary Breast Sarcoma: A Retrospective Study From Single Institute in China.

Primary breast sarcomas (PBSs) are spectrum heterogeneous sarcomas in breast and the optimal treatment for them is still under discussion. Our study was to investigate clinical characteristics and identify potential prognostic factors for this rare malignancy. The authors retrospectively reviewed 38 patients with PBSs between October 2000 and February 2014 in FuDan University Shanghai Cancer Center. Local control rate and overall survival (OS) were determined by Kaplan-Meier actuarial method. Univariate analysis and Cox proportional hazards model were applied to identify potential prognostic factors. With median follow-up of 40.19 months, 14 patients (14/38) were found with local recurrence. Extensive operation like mastectomy was not superior to local resection (P = 0.167). Three-year recurrence-free survival and OS rate were 61.9% and 89%, respectively. Larger tumor size and local recurrence were indicated as unfavorable prognostic factors in univariate analysis. Cox model identified narrow interval of recurrence free survival as an unfavorable factor (P = 0.048). Surgery remains crucial treatment for PBSs. Mastectomy, however, is not routinely necessary if clear margin could be achieved by local excision. Early recurrence indicates a poor OS.

Early cardiac toxicity following adjuvant radiotherapy of left-sided breast cancer with or without concurrent trastuzumab.

PURPOSE: To evaluate the influence of concurrent trastuzumab on the cardiotoxicity in patients receiving left-sided adjuvant radiotherapy. MATERIALS AND METHODS: Medical records of stage I-III left-sided breast cancer patients, including 64 receiving concurrent trastuzumab with radiotherapy and 73 receiving radiotherapy alone were retrospectively reviewed. All of the patients had normal LVEF after adjuvant chemotherapy. Information of doses volume to cardiac structures was collected. Cardiac events were assessed according to CTC 2.0. RESULTS: Median follow-up of LVEF and clinical assessment of cardiac function from the initiation of radiotherapy was 6.7 months (range 3-60.9) and 26 months (range 6.4-60.9), respectively. Grade 1 LVEF dysfunction occurred in 5 (7.8%) and 3 (4.1%) patients of the concurrent-trastuzumab and radiotherapy alone cohort, respectively. Trastuzumab was the only significant factor influencing absolute LVEF decrease in univariate analysis. In multivariate analysis of concurrent-trastuzumab cohort, IMC radiotherapy and start trastuzumab during radiotherapy were independent risk factors. For concurrent cohort, mean heart dose, as well as D10-D30, D50-D55, V5-V20 of the heart and D30-D45, D65-D75, V6-V15 of the LV were significantly higher in patients developing LVEF dysfunction. CONCLUSIONS: Concurrent trastuzumab and left-sided radiotherapy is well tolerated in terms of cardiotoxicity in patients with normal baseline cardiac function after adjuvant chemotherapy. However, increases in mean dose and low-dose volume of cardiac structures are associated with a higher risk of acute LVEF dysfunction.

Management experiences of primary angiosarcoma of breast: a retrospective study from single institute in the People's Republic of China.

BACKGROUND: Primary angiosarcoma of breast (PAOB) is a rare and highly aggressive malignancy. There is no general agreement on optimal treatments or prognostic factors for this orphan disease. The objective of this study was to investigate the clinicopathologic features and management experiences of PAOB. METHODS: We performed a retrospective review of medical and pathologic records of 17 consecutive patients diagnosed with PAOB between January 2000 and February 2014 at FuDan University Shanghai Cancer Center. We evaluated the clinical characteristics, multimodality treatments, and associated clinical outcomes. RESULTS: A total of 16 patients were included in this retrospective study (median age at PAOB presentation 33.5 years, range: 19-56 years). Palpable tumor with or without breast skin ecchymosis presented as the most common initial symptom. All patients underwent surgery with curative intent. Median disease-free survival and overall survival (OS) were 9 months and 13.6 months, respectively. One-year and 3-year disease-free survival rates were 43.8% and 6.3%, with OS rates of 93.8% and 78.1%, respectively. High histologic grade indicated poorer OS by univariate analysis (P=0.01). However, neither adjuvant chemotherapy nor radiotherapy contributed to clinical outcomes in our series. CONCLUSION: PAOB is considered as an infrequent breast neoplasm with aggressive characteristics. Histologic grade and early metastasis (within 12 months after diagnosis) are associated with poor prognosis. Regardless of grade, additional benefit was not observed with adjuvant therapy.

Dose coverage of axillary level I-III areas during whole breast irradiation with simplified intensity modulated radiation therapy in early stage breast cancer patients.

PURPOSE: This study was designed to evaluate the dose coverage of axillary areas during whole breast irradiation with simplified intensity modulated radiation therapy (s-IMRT) and field-in-field IMRT (for-IMRT) in early stage breast cancer patients. METHODS: Sixty-one consecutive patients with breast-conserving surgery and sentinel lymph node biopsy were collected. Two plans were created for each patient: the s-IMRT and for-IMRT plan. Dosimetric parameters of axillary areas were compared. RESULTS: The average of mean doses delivered to the axillary level I areas in s-IMRT and for-IMRT plan were 27.7Gy and 29.1Gy (p = 0.011), respectively. The average of V47.5Gy, V45Gy and V40Gy (percent volume receiving≥ 47.5Gy, 45Gy and 40Gy) of the axillary level I in s-IMRT plan was significantly lower than that in for-IMRT plan (p < 0.001). For for-IMRT plans, patients with upper tangential border to humeral head ≤2cm, breast separation >19.3cm and body width >31.9cm had significantly higher mean dose in axillary level I area (p = 0.002, 0.007, 0.001, respectively). CONCLUSION: Compared with for-IMRT plan, the s-IMRT plan delivered lower dose to axillary level I area. For centers using s-IMRT technique, caution should be exercised when selecting to omit axillary lymph node dissection for patients with breast conserving surgery and limited positive SLNs.

Diastolic Dysfunction Occurs Early in HER2-Positive Breast Cancer Patients Treated Concurrently With Radiation Therapy and Trastuzumab.

BACKGROUND: Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular diastolic dysfunction (LVDD) and its relationship to the dose-volume of the heart irradiated were evaluated in HER2-positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT). MATERIALS AND METHODS: Data from 40 breast cancer patients treated with concurrent trastuzumab and left-sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right-sided adjuvant RT and 71 patients treated with left-sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified. RESULTS: Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left-sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. Dmean, D15-D40, D60-D70, and V3-V10 of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left-sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left-sided RT alone. CONCLUSION: Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose-volume of the heart contributes significantly to the risk of LVDD in patients with left-sided breast cancer treated concurrently with trastuzumab. IMPLICATIONS FOR PRACTICE: Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose-volume of the heart irradiated in patients with left-sided breast cancer receiving radiotherapy concurrently with trastuzumab. This result highlights the importance of decreasing the dose-volume of heart irradiated as a protective strategy in the treatment setting of concurrent trastuzumab and radiotherapy. Diastolic dysfunction may serve as a more sensitive tool for the early detection of cardiac damage and should be incorporated as a routine parameter in the functional monitoring of cardiotoxicity.