[en] Purpose: There is a paucity of data regarding prognostic implications of having LCIS as a histologic component of invasive breast carcinomas or ductal carcinoma in situ. The purpose of this study is to assess the long term outcome of patients with breast carcinoma with a component of LCIS, treated with conservative surgery and radiation therapy. Materials and Methods: The pathology reports of all patients treated with conservative surgery and radiation therapy at our institution prior to 1993 were reviewed to identify patients who had LCIS as a histologic component. A total of 51 patients were identified. Primary histology of the 51 patients were as follows: 53% infiltrating lobular, 20% invasive and intraductal, 18% invasive ductal, 10% intraductal. There were no patients treated who had LCIS only. 1023 patients treated conservatively during the same time interval without LCIS served as a control group. All patient characteristics, staging, treatment and outcome variables were entered into a computer database. Overall survival, disease-free survival, local-regional relapse and distant metastasis rates were calculated from the date of diagnosis to the most recent follow-up. Results: As of (3(96)), the median follow-up for the LCIS containing group and control group was 10.6 and 11.4 years, respectively. There were no significant differences in age of presentation, clinical stage, nodal status, estrogen receptor status, or adjuvant therapy received between the two groups. Twenty-two patients (43%) in the LCIS group underwent re-excision. Of those, 68% had residual LCIS in the re-excision specimen. LCIS was characterized as focal in 29%, diffuse in 25%, and not specified in all other cases. Forty-one percent of patients with LCIS containing tumors had a positive family history. The primary histology of the two populations differed significantly with a larger percentage of infiltrating lobular primaries in the LCIS group (53% vs. 4%, p<.001). The LCIS group also differed from the control group with respect to the percentage of patients with bilateral disease (17% vs. 8%, p=0.052), and the percentage of patients with 'false negative' mammograms (20% vs. 10%, p=0.002). There was no statistically significant difference between the LCIS group and control group in the 10 year overall survival (67% vs. 72%), distant disease free survival (62% vs. 79%) or relapse free survival (50% vs. 68%). Of note, the 10 year ipsilateral breast tumor recurrence free survival between the two groups was not significantly different (77% LCIS vs. 84% control). Conclusion: Patients with lobular carcinoma in situ as a histological component of breast cancer do not carry a worse prognosis than breast cancer patients without an LCIS component. Furthermore, the comparable local control rates between conservatively treated patients with or without LCIS suggests that patients with a histologic component of LCIS are suitable candidates for conservative surgery and radiation therapy

[en] Purpose: To examine the local control, survival and complications in patients treated with brachytherapy for recurrent or persistent carcinoma of the nasopharynx. Materials and Methods: Eighteen brachytherapy procedures for recurrent nasopharyngeal carcinoma and four interstitial implants for persistent disease after primary therapy were performed on 21 patients at Memorial Sloan-Kettering Cancer Center between 1986 and 1992. Permanent implants with I-125 seeds, via a transnasal, transoral or transpalatal approach, were used in patients with discrete, well-demarcated lesions. Intracavitary Ir-192 or high activity I-125 were used for patients with diffuse lesions, laterally situated lesions or those involving the nasal cavity. Ten patients with recurrent, diffuse disease also received EBRT (25-54 Gy) as part of their salvage treatment. All patients were followed up to the present time or time of death (median 14 mo.). Results: Of the patients with recurrent disease, 41% are alive at 2 years with 29% locally controlled. Forty seven percent of all patients with recurrent disease remain alive 18-114 months post-treatment (median 48 mo.). Twenty nine percent are NED at a median of 49 months (range 32-89 mo.). Of the patients with persistent disease, three of the four are NED at 47, 85, 87 months. There was no statistical difference in local control or survival in respect to histology, gender, time to recurrence, age, mode of treatment (intracavitary vs. interstitial), or the addition of external beam to the salvage therapy. All 22 procedures were tolerated well without complications in the operative/immediate post-operative period. The overall severe complication rate in the follow-up period was 19%: severe mucositis(n=2), bone necrosis(n=1) and hearing loss(n=2). Conclusion: The brachytherapy techniques we have utilized are feasible and appear safe. Local control is obtainable in this group of patients with acceptable toxicity. Implant techniques should be individualized to the exact anatomic and oncologic situation

No abstract available

[en] The goal of this work is to present a systematic Monte Carlo validation study on the clinical implementation of the enhanced dynamic wedges (EDWs) into the Pinnacle³ (Philips Medical Systems, Fitchburg, WI) treatment planning system (TPS) and QA procedures for patient plan verification treated with EDWs. Modeling of EDW beams in the Pinnacle³ TPS, which employs a collapsed-cone convolution superposition (CCCS) dose model, was based on a combination of measured open-beam data and the 'Golden Segmented Treatment Table' (GSTT) provided by Varian for each photon beam energy. To validate EDW models, dose profiles of 6 and 10 MV photon beams from a Clinac 2100 C/D were measured in virtual water at depths from near-surface to 30 cm for a wide range of field sizes and wedge angles using the Profiler 2 (Sun Nuclear Corporation, Melbourne, FL) diode array system. The EDW output factors (EDWOFs) for square fields from 4 to 20 cm wide were measured in virtual water using a small-volume Farmer-type ionization chamber placed at a depth of 10 cm on the central axis. Furthermore, the 6 and 10 MV photon beams emerging from the treatment head of Clinac 2100 C/D were fully modeled and the central-axis depth doses, the off-axis dose profiles and the output factors in water for open and dynamically wedged fields were calculated using the Monte Carlo (MC) package EGS4. Our results have shown that (1) both the central-axis depth doses and the off-axis dose profiles of various EDWs computed with the CCCS dose model and MC simulations showed good agreement with the measurements to within 2%/2 mm; (2) measured EDWOFs used for monitor-unit calculation in Pinnacle³ TPS agreed well with the CCCS and MC predictions within 2%; (3) all the EDW fields satisfied our validation criteria of 1% relative dose difference and 2 mm distance-to-agreement (DTA) with 99-100% passing rate in routine patient treatment plan verification using MapCheck 2D diode array.

[en] Purpose: To compare the clinical-pathologic features and long-term outcomes for women with ductal carcinoma in situ (DCIS) vs. DCIS with microinvasion (DCISM) treated with breast conservation therapy (BCT), to assess the impact of microinvasion. Patients and Methods: A total of 393 patients with DCIS/DCISM from our database were analyzed to assess differences in clinical-pathologic features and outcomes for the two cohorts. Results: The median follow-up was 8.94 years, and the mean age was 55.8 years for the entire group. The DCISM cohort was comprised of 72 of 393 patients (18.3%). Surgical evaluation of the axilla was performed in 58.3% (n = 42) of DCISM vs. 18.1% (n = 58) of DCIS, with only 1 of 42 DCISM (2.3%) vs. 0 of 58 DCIS with axillary metastasis. Surgical axillary evaluation was not an independent predictor of local-regional relapse (LRR), distant relapse-free survival (DRFS), or overall survival (OS) in Cox proportional hazards analysis (p > 0.05). For the DCIS vs. DCISM groups, respectively, the 10-year breast relapse-free survival was 89.0% vs. 90.7% (p = 0.36), DRFS was 98.5% vs. 97.9% (p = 0.78), and OS was 93.2% vs. 95.7% (p = 0.95). The presence of microinvasion did not correlate with LRR, age, presentation, race, family history, margin status, and use of adjuvant hormonal therapy (all p > 0.05). In univariate analysis, pathology (DCIS vs. DCISM) was not an independent predictor of LRR (hazard ratio [HR], 1.58; 95% confidence interval [CI], 0.58–4.30; p = 0.36), DRFS (HR, 0.72; 95% CI, 0.07–6.95; p = 0.77), or OS (HR, 1.03; 95% CI, 0.28–3.82; p = 0.95). Conclusions: Our data imply that the natural history of DCISM closely resembles that of DCIS, with a low incidence of local-regional and distant failures. On the basis of our large dataset, the incidence of axillary metastasis in DCISM appears to be small and not appear to correlate to outcomes, and thus, microinvasion alone should not be the sole criterion for more aggressive treatment.

[en] Purpose: To evaluate our institutional experience of treating tubular carcinoma of the breast (TC) and invasive ductal carcinoma (IDC) with conservative surgery and radiation therapy, to compare clinical-pathologic features and long-term outcomes. Methods and Materials: A review of our institution's tumor registry from 1975 to 2007, followed by a central pathology review of available slides, yielded 71 cases of Stage I/II TC and 2,238 cases of Stage I/II IDC treated with breast conservation therapy. Clinical-pathologic features and outcomes were analyzed by subtype to detect significant differences. Results: The median follow-up was 7 years. The TC cohort presented more frequently with pT1 disease (97% vs. 80%, p = 0.0007), pN0 disease (95% vs. 74%, p = 0.0004), hormone-receptor positivity (ER+, 89% vs. 62%, p = 0.0001; PR+, 81% vs. 52%, p = 0.0001), and HER-2 negativity (89% vs. 71%, p = 0.04). Clinical outcomes also favored the TC cohort, with lower rates of breast cancer-related death (1% vs. 10%; p = 0.0109) and distant metastasis (1% vs. 13%; p = 0.0028) and higher rates of 10-year overall (90% vs. 80%; p = 0.033), cause-specific (99% vs. 86%; p = 0.011), and disease-free (99% vs. 82%; p = 0.003) survival. There was a nonsignificant trend toward improved breast cancer relapse-free survival for the TC cohort (95% vs. 87%; p = 0.062) but no difference in nodal relapse-free survival or contralateral breast cancer relapse-free survival (all p values >0.05) between the cohorts. Conclusion: Our institutional experience suggests that TC, when compared with IDC, is associated with more favorable clinical-pathologic features and comparable, if not superior, outcomes after breast conservation therapy, suggesting the appropriateness of a conservative approach to this rare subtype.

[en] Background: Insulin-like growth factor (IGF) receptor is a key receptor in apoptotic protection, cell adhesion, longevity, and transformation into a cancerous cell and can induce malignant changes in the presence of the IGF ligand. Over-expression of IGF-1R has been associated with resistance to radiation. Inhibitors of IGF-1R have been shown to enhance tumor radiation sensitivity and amplify radiation therapy-induced apoptosis. The purpose of this study is to evaluate the prognostic significance of IGF-1R expression in patients with breast cancer treated with breast conserving therapy. Materials and methods: Paraffin specimens from 345 women with early stage breast cancer treated with BCT were constructed into tissue microarrays and stained for IGF-1R, COX-2 and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between IGF-1R, other co-variables, and outcome was assessed. Results: IGF-1R over-expression was identified in 197 cases (57%). IGF-1R over-expression was found to be correlated with African-American race (p = 0.0233), p53 status (p = 0.0082) and COX-2 expression (p < 0.0001). While IGF-1R over-expression was associated with lower overall survival (p = 0.0224) in node-negative patients, there was no impact of IGF-1R expression on local control. Conclusions: In node-negative patients, patients with high levels of IGF-1R were found to have a significant reduction in overall survival, but no apparent effect on local control. Given the limited published data on IGF-1R in early stage, conservatively treated patients, further studies investigating IGF-1R expression in this cohort are necessary.

[en] Purpose: To compare mammographically occult (MamOcc) and mammographically positive (MamPos) early-stage breast cancer patients treated with breast-conservation therapy (BCT), to analyze differences between the two cohorts. Methods and Materials: Our two cohorts consisted of 214 MamOcc and 2168 MamPos patients treated with BCT. Chart reviews were conducted to assess mammogram reports and method of detection. All clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. Results: Median follow-up was 7 years. There were no differences in final margins, T stage, nodal status, estrogen/progesterone receptor status, or 'triple-negative' status. Significant differences included younger age at diagnosis (p < 0.0001), more positive family history (p = 0.0033), less HER-2+ disease (p = 0.0294), and 1^o histology (p < 0.0001). At 10 years, the differences in overall survival, cause-specific survival, and distant relapse between the two groups did not differ significantly. The MamOcc cohort had more breast relapses (15% vs. 8%; p = 0.0357), but on multivariate analysis this difference was not significant (hazard ratio 1.0, 95% confidence interval 0.993-1.007, p = 0.9296). Breast relapses were mammographically occult in 32% of the MamOcc and 12% of the MamPos cohorts (p = 0.0136). Conclusions: Although our study suggests that there are clinical-pathologic variations for the MamOcc cohort vs. MamPos patients that may ultimately affect management, breast relapse after BCT was not significantly different. Breast recurrences were more often mammographically occult in the MamOcc cohort; consideration should be given to closer follow-up and alternative imaging strategies (ultrasound, breast MRI) for routine posttreatment examination. To our knowledge, this represents the largest series addressing the prognostic significance of MamOcc cancers treated with BCT.

[en] 

Purpose

Despite delays between diagnosis and surgery adversely affecting survival, patients frequently transfer their breast cancer care between institutions. This study was performed to assess the prevalence and effect of such transfers of care (TsOC) on the time to surgery, and its impact on current time-dependent breast cancer quality metrics at Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (NAPBC)-accredited institutions.

Methods

Patients having non-metastatic invasive breast cancer diagnosed between 2006 and 2015 at CoC and NAPBC centers (“reporting facilities”) in the National Cancer Database were reviewed. TsOC refer to transferring into or out of a reporting facility between diagnosis and surgery.

Results

Among 622,793 patients, 36.6% of patients transferred care. TsOC add 7.3, 7.8, 8.7, and 9.8 days in time to surgery, chemotherapy, radiotherapy, and endocrine therapy, respectively (p’s < 0.0001). On multivariable analysis, the odds of surgery occurring > 90 days from diagnosis were greatest for patients undergoing unilateral or bilateral mastectomy, Black or Hispanic patients, and those having TsOC (ORs > 1.73, p’s < 0.0001). TsOC increase the odds of non-compliance, per patient, for chemotherapy, radiotherapy and endocrine therapy time-dependent measures by 65.4%, 25.6%, and 56.5%, respectively (p < 0.0001).

Conclusions

TsOC for newly diagnosed breast cancers to or from an accredited facility result in delays in time to surgery which can affect compliance with time-dependent quality measures. Facilities frequently receiving transferred patients may be most adversely affected. Although non-compliance with these quality measures is low, institutions and accrediting bodies should be aware of these associations in order to comply with time-dependent standards.

[en] Purpose: To evaluate the prognostic significance of cyclooxygenase-2 (COX-2) in breast cancer patients treated with conservative surgery and radiation therapy (CS+RT). Methods and Materials: Between 1975 and 2003, we retrieved specimens from 504 breast cancer patients treated with CS+RT. The specimens were constructed into tissue microarrays processed and stained for estrogen receptor (ER), progesterone receptor, Her2/neu, and COX-2. Each core was scored as positive or negative. All data including demographics, clinical, pathologic, staging, and outcome variables were entered into a computerized database. Results: Expression of COX-2 was positive in 58% of cases and correlated with younger age (p = 0.01) and larger tumor size (p 0.001). Expression of COX-2 was predictive of local relapse (relative risk[RR], 3.248; 95% confidence interval [CI], 1.340-7.871; p = 0.0091), distant metastasis (RR, 2.21; 95% CI, 1.259-3.896; p = 0.0058), and decreased survival (RR, 2.321; 95% CI, 1.324-4.071; p = 0.0033). Among ER-positive patients, COX-2 expression was predictive of worse local control (85% vs. 93%, p = 0.04), distant metastasis (75% vs. 95%, p = 0.002) and worse survival (65% vs. 94%, p = 0.002). Among ER-negative tumors COX-2 expression was not significantly correlated with local control (87 vs. 95%, p = 0.12), distant metastasis (73% vs. 78%, p = 0.39), or survival (77% vs. 87%, p 0.15). Conclusions: In breast cancer patients treated with CS+RT, COX-2 expression is associated with younger age, larger tumor size, worse local control, distant metastasis, and worse overall survival. The significance is limited to hormone receptor-positive tumors, consistent with the known effect of COX-2/PGE2 on aromatase activity. Use of COX-2 inhibitors in estrogen-dependent breast cancers warrants further investigation