The impact of loco-regional treatment modality on the outcomes in breast cancer patients younger than forty years of age.

PURPOSE: To determine the impact of the loco-regional treatment modality, on the loco-regional recurrence (LRR) rates and overall survival (OS) in breast cancer patients younger than 40 years. METHODS: Data of 623 breast cancer patients younger than 40 years of age were retrospectively reviewed. Patients were stratified according to the locoregional treatment approach into three groups: the mastectomy group (M), the mastectomy followed by radiation therapy group (MRX) and the breast conservative therapy group (BCT). RESULTS: Median follow-up was 72 months (range, 6-180). Two hundred and nine patients were treated with BCT, 86 with MRM and 328 with MRX. The 10-year rate LRR rates according to treatment modality were: 13.4% for BCT, 15.1% for MRM and 8.5% for MRX (p 0.106). On univariate analysis, T stage (p 0.009), AJCC stage (p 0.047) and Her 2 status (p 0.001) were associated with LRR. Ten-year overall survival (OS) was 72.7% (78.5% in the BCT group, 69.8% in the MRM group and 69.8% in the MRX group, p 0.072). On Univariate analysis, age < 35 (p 0.032), grade III (p 0.001), N3 stage (p 0.001), AJCC stage III (p 0.005), ER negative status (0.04), Her 2-status positive (0.006) and lack of chemotherapy administration (p 0.02) were all predictors of increased mortality. CONCLUSION: For patients younger than 40 years of age, similar LRR and overall survival outcomes were achieved using BCT, M or MRX. Young age at diagnosis should not be used alone in recommending one loco-regional treatment approach over the others.

Phyllodes tumors of the breast: Adjuvant radiation therapy revisited.

BACKGROUND: Phyllodes tumors (PT) are rare entity and surgical resection is the cornerstone of treatment. No standard of care exists regarding adjuvant treatment especially radiation therapy (RT). PATIENTS AND METHODS: We analyzed all patients with non-metastatic, resected phyllodes tumors who presented to our institution from January 2005 through December 2019. Primary study endpoints included local recurrence free survival (LRFS) and overall survival (OS). RESULTS: One hundred and eight patients were analyzed (patients with incomplete treatment and follow up data were excluded). Fifty patients had benign phyllodes, 26 patients had borderline and 32 patients had malignant phyllodes. In the benign group, no significant difference in LRFS was observed between patients who received adjuvant RT (n = 3) and those who did not (5-year LRFS 100% vs. 85% respectively, p = 0.49). The 5 year OS for patients who received RT was 60% vs. 89% for those who did not (p 0.40). In the borderline/malignant group, adjuvant RT significantly improved five year LRFS (90% in the RT group vs. 42% in the no RT group, p = 0.005). The 5 year LRFS in patients treated with margin negative breast conserving surgery and RT was 100% vs. 34.3% in patients who did not receive RT (p 0.022). Patients treated with mastectomy and RT had a 5 year LRFS of 100% vs. 83% for patients who did not receive RT (p 0.24). On multivariate analysis, radiation therapy was independently associated with decreased hazard of local failure (HR 0.21, CI 0.05-0.89, p = 0.03). No difference in OS was found between the RT and no RT groups (5-year OS was 52% vs. 45% respectively, p 0.54). CONCLUSION: The results of the current study confirm the excellent prognosis of benign phyllodes tumors; warranting no further adjuvant treatment after margin-negative surgical resection. For patients with borderline/malignant phyllodes tumors, adjuvant radiation therapy significantly improved LRFS after margin negative wide local excision; however, patients treated with mastectomy did not attain the same benefit from adjuvant irradiation.

Once Daily Versus Twice Daily External Beam Accelerated Partial Breast Irradiation: A Randomized Prospective Study.

PURPOSE: The aim of the current study was to compare toxicity, cosmesis, and local control between the once daily and the twice daily fractionation schemes for external beam accelerated partial breast irradiation. METHODS AND MATERIALS: From December 2012 to June 2018, we enrolled 113 patients with ductal carcinoma in situ or invasive breast cancer, node negative disease, and tumors less than 3 cm in size to receive accelerated partial breast irradiation (APBI) to a total dose of 38.5 Gy over 10 fractions given either once (oAPBI) or twice daily (tAPBI). Sixty patients were included in the tAPBI arm and 53 patients were included in the oAPBI arm. RESULTS: Median follow-up was 74 months (range, 24-105). The median pain score during treatment was 3 out of 10 in the oAPBI and 5 in the tAPBI (P = .001). No differences were observed in GIII early skin toxicity (P = .4) or GI early pulmonary toxicity (P = 1.0) between the 2 treatment arms. GIII late skin toxicity developed in 3.8% and 11.7% of patients in the oAPBI and tAPBI arms, respectively (P = .001). GIII subcutaneous fibrosis developed in 1.9% and 8.3% of patients in the oAPBI and tAPBI, respectively (P = .001). The rate of patients with adverse cosmesis (poor/fair) was 7.5% at 12 months and at 24 months in the oAPBI arm compared with 21.7% and 26.7% in the tAPBI arm (P = .03 and .008, respectively). CONCLUSIONS: oAPBI is a safe, well-tolerated schedule with more favorable outcomes than the tAPBI schedule with regards to late toxicity and cosmesis.

Phyllodes Tumors of the Breast (the Egyptian Experience).

Phyllodes tumors (PT) are rare fibroepithelial lesions, about 0.3-0.5% of all breast tumors. This study is an evaluation of patient characteristics, clinicopathologic features, diagnostic tools, therapeutic options, risk factors for recurrence, and distant metastasis and follow-up findings in patients with PTs. One hundred twenty-seven patients with pathologically proved PTs in the National Cancer Institute, Cairo University, Egypt, from January 2011 to January 2016 were reviewed and analyzed. Sixty patients presented with benign PTs (47.2%), 34 had borderline PTs (26.8%), and 33 had malignant PTs (26%). The mean follow-up period was approximately 36 months; local recurrence occurred in 34 patients, 9 benign cases (14.5%), 11 borderlines (32.4%), and 14 malignant PTs (42.4%). Mastectomy was the most commonly used surgery in recurrent cases (61.4%). Axillary staging was performed in 31 cases (24.4%); only 2 cases showed positive nodal metastasis (6.5%) and were of the malignant subtype. Distant metastasis occurred in 12 patients, 4 with borderline PTs, and 8 with malignant PTs. The most common site for metastasis was the lungs and bones. Adjuvant radiotherapy was applied in 9 patients, 2 in borderline phyllodes, and 7 in malignant phyllodes; post-radiotherapy recurrence occurred in 5 malignant phyllodes patients. Chemotherapy was employed in 10 metastatic patients (4 with borderline and 6 with malignant phyllodes); excision with clear margins is important to reduce the local recurrence. Routine axillary staging should not be done. The adjuvant radiation therapy is still controversial. Local recurrence can develop even after appropriate surgery. Therefore, close follow-up is mandatory.

Circulating tumor cells as predictors of response and failure in breast cancer patients treated with preoperative chemotherapy.

AIM: To explore the significance of circulating tumor cells (CTCs) detection in the course of preoperative chemotherapy (PC) and their effect on the outcomes.
 METHODS: Fifty-five patients with stage II/III invasive breast cancer were enrolled into a preoperative clinical trial. Patients were given PC with sequential single-agent doxorubicin and paclitaxel vs paclitaxel followed by doxorubicin. Blood samples (8 mL) were collected from patients before PC, after each phase, and at 6 months intervals during follow-up. Peripheral blood mononuclear cells were isolated and enriched for epithelial cells. Quantitative RT-PCR was used to determine the presence of cytokeratin 19 (CK19) mRNA. Samples were considered positive when the PCR curve crossed the standard threshold curve.
 RESULTS: After the first phase of chemotherapy, there was a 59% overall reduction in the median tumor volume. The percentage of volume reduction did not differ between patients who presented with detectable CTCs at baseline and those who did not (p=0.89). After the second phase of chemotherapy, there was a further decrease in the median tumor volume to 93% from baseline. There was no correlation between the lack of response and the presence of CTCs either after the first (p=0.36) or second (p=0.5391) phases of PC. The presence of CTCs was a predictor of local or distant relapse (p=0.0411). The detection of CTCs did not affect overall survival (p=0.2569).
 CONCLUSION: CTCs can be used as predictors of relapse after definitive treatment of locally advanced breast cancer; however, CTCs detection in peripheral blood during the course of PC does not implicate a particular pattern of response to treatment.

Post mastectomy radiation for large node negative breast cancer: time for a second look.

Patients with node negative and large primary tumors ≥5cm comprise a rare entity of breast cancer patients for which clear management guidelines are not available. Data about the rates of loco-regional failures (LRF) in this patient population are scarce and reporting widely varying observations. Post Mastectomy Radiation Therapy (PMRT) for this group of patients is controversial. In this review we examined the available literature discussing the LRF rates in this clinical setting and the value of adding PMRT in their management.

Patterns and risk factors of locoregional recurrence in T1-T2 node negative breast cancer patients treated with mastectomy: implications for postmastectomy radiotherapy.

PURPOSE: Postmastectomy radiation therapy (PMRT) can reduce locoregional recurrences (LRR) in high-risk patients, but its role in the treatment of lymph node negative (LN-) breast cancer remains unclear. The aim of this study was to identify a subgroup of T1-T2 breast cancer patients with LN- who might benefit from PMRT. METHODS AND MATERIALS: We retrospectively reviewed 1,136 node-negative T1-T2 breast cancer cases treated with mastectomy without PMRT at the Massachusetts General Hospital between 1980 and 2004. We estimated cumulative incidence rates for LRR overall and in specific subgroups, and used Cox proportional hazards models to identify potential risk factors. RESULTS: Median follow-up was 9 years. The 10-year cumulative incidence of LRR was 5.2% (95% CI: 3.9-6.7%). Chest wall was the most common (73%) site of LRR. Tumor size, margin, patient age, systemic therapy, and lymphovascular invasion (LVI) were significantly associated with LRR on multivariate analysis. These five variables were subsequently used as risk factors for stratified analysis. The 10-year cumulative incidence of LRR for patients with no risk factors was 2.0% (95% CI: 0.5-5.2%), whereas the incidence for patients with three or more risk factors was 19.7% (95% CI: 12.2-28.6%). CONCLUSION: It has been suggested that patients with T1-T2N0 breast cancer who undergo mastectomy represent a favorable group for which PMRT renders little benefit. However, this study suggests that select patients with multiple risk factors including LVI, tumor size ≥2 cm, close or positive margin, age ≤50, and no systemic therapy are at higher risk of LRR and may benefit from PMRT.

A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic bladder cancer.

BACKGROUND: Zoledronic acid treatment reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from breast, lung, and urologic cancers including prostate and renal cancer. The aim of this study was to evaluate the effect of zoledronic acid on SREs in patients with bone metastases from bladder cancer. PATIENTS AND METHODS: Patients with bone metastases from bladder cancer who were receiving palliative radiotherapy were randomized to placebo or zoledronic acid (4 mg intravenous monthly) for 6 months. RESULTS: The patients (n = 40) were evenly distributed between the two treatment groups, and the baseline demographics of the two groups were similar. The follow-up varied from 8 to 65 weeks (median 24 weeks). Compared with patients receiving placebo, those receiving zoledronic acid had a lower mean incidence of SREs (2.05 +/- 1.0 vs. 0.95 +/- 0.9, respectively), and a larger proportion did not experience an on-study SRE (2 vs. 8 patients, respectively). Zoledronic acid also prolonged the median time to first SRE compared with the placebo (16 vs. 8 weeks, respectively). Multiple event analysis of SREs revealed that zoledronic acid decreased the risk of SRE development by 59% (hazard ratio 0.413). Zoledronic acid also increased the 1-year survival rate compared with placebo (36.3 +/- 11.2 vs. 0%, respectively). Zoledronic acid was generally well tolerated in our patient population. CONCLUSIONS: Zoledronic acid therapy decreased the incidence of SREs and improved the 1-year survival rate of patients with bone metastases from bladder cancer, potentially through its anticancer activity.

Does lymphovascular invasion predict regional nodal failure in breast cancer patients with zero to three positive lymph nodes treated with conserving surgery and radiotherapy? Implications for regional radiation.

PURPOSE: To examine the relationship between lymphovascular invasion (LVI) and regional nodal failure (RNF) in breast cancer patients with zero to three positive nodes treated with breast-conservation therapy (BCT). METHODS AND MATERIALS: The records of 1,257 breast cancer patients with zero to three positive lymph nodes were reviewed. All patients were treated with BCT at Massachusetts General Hospital from 1980 to December 2003. Lymphovascular invasion was diagnosed by hematoxylin and eosin-stained sections and in some cases supported by immunohistochemical stains. Regional nodal failure was defined as recurrence in the ipsilateral supraclavicular, axillary, or internal mammary lymph nodes. Regional nodal failure was diagnosed by clinical and/or radiologic examination. RESULTS: The median follow-up was 8 years (range, 0.1-21 years). Lymphovascular invasion was present in 211 patients (17%). In univariate analysis, patients with LVI had a higher rate of RNF (3.32% vs. 1.15%; p = 0.02). In multivariate analysis, only tumor size, grade, and local failure were significant predictors of RNF (p = 0.049, 0.013, and 0.0001, respectively), whereas LVI did not show a significant relationship with RNF (hazard ratio = 2.07; 95% CI, 0.8-5.5; p = 0.143). The presence of LVI in the T2/3 population did not increase the risk of RNF over that for those with no LVI (p = 0.15). In addition, patients with Grade 3 tumors and positive LVI did not have a higher risk of RNF than those without LVI (p = 0.96). CONCLUSION: These results suggest that LVI can not be used as a sole indicator for regional nodal irradiation in breast cancer patients with zero to three positive lymph nodes treated with BCT.