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Lawrence J Solin

Publications and source records attributed to Lawrence J Solin.

At least 19 recordsLinked to original sources

Extensive retraction artifact correlates with lymphatic invasion and nodal metastasis and predicts poor outcome in early stage breast carcinoma.

Retraction artifact resulting in clear spaces around tumor cell nests is frequently seen in histologic material and may present difficulty in their differentiation from lymphovascular invasion. We noticed that retraction artifact seemed to be more common around groups of breast cancer cells compared with benign acini, and when extensively present, metastasis to axillary lymph nodes was often seen. Thus, we performed a study of 304 cases of stage pT1 and pT2 breast carcinomas to test our hypothesis that extensive retraction artifact in tumors correlates with lymphatic spread and outcome. Tumors were evaluated to determine the presence and extent of retraction artifact around tumor cell nests and the presence of lymphatic invasion. Lymphatic invasion was confirmed by D2-40 immunostaining. The extent of retraction artifact in tumors was correlated with clinicopathologic tumor features and patient outcome. Variable degree of retraction artifact was present in 183 of 304 (60%) invasive carcinomas, with its extent ranging from 0% to 90% (median 5%). The extent of retraction artifact showed a significant correlation with tumor size, histologic type, histologic grade, presence of lymphovascular invasion, and nodal metastasis. Further, extensive retraction artifact was significantly associated with poor overall and disease-free survival in both univariate and multivariate analyses. We propose that the apparent retraction of the stroma from cells of invasive breast carcinoma on routine histologic sections is not a phenomenon merely due to inadequate fixation as currently believed. Rather, it likely signifies important biologic changes that alter tumor-stromal interactions and contribute to lymphatic spread and tumor progression.

Artifacts↗

Twenty-year incidence and patterns of contralateral breast cancer after breast conservation treatment with radiation.

PURPOSE: This study was undertaken to determine the incidence of contralateral breast cancer (CLB) after treatment for early-stage breast cancer with breast-conserving treatment (BCT), and to observe patterns of CLB presentation. METHODS: Medical records of 1,801 women treated for unilateral AJCC Stage 0-II breast cancer with BCT between 1977 and 2000 were analyzed as a retrospective cohort. RESULTS: The incidence of any CLB at 20 years was 15.4%. The annual risk of developing any CLB remained constant at approximately 0.75% per year after treatment. The median time to any CLB was 8.2 years (range, 0.5-26.5 years). No difference in incidence of CLB was demonstrated in patients with primary invasive carcinoma vs. DCIS (p = 0.84). The majority of patients (83%) developing CLB tumors developed invasive disease. The risk of developing an invasive CLB did not differ significantly for patients with DCIS vs. those with primary invasive carcinoma (p = 0.20). The method of detection of the primary tumor (mammography vs. physical examination) was not predictive of detection of the CLB (p = 0.20). Finally, the location of CLB tumors was not affected by that of prior tumors (p = 0.82). CONCLUSIONS: The risk of development of CLB persists for at least 20 years after treatment for early-stage breast cancer. CLB tumors are frequently invasive, and their location is not influenced by location of prior tumors. Mammography and physical examination remain essential after BCT for detection of a contralateral breast cancer, regardless of the method of detection of the primary tumor.

Adult↗

Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment.

PURPOSE: Several studies have reported increased cardiac mortality related to the use of left-sided breast or chest-wall irradiation. This study was undertaken as a comprehensive examination of the long-term cardiac mortality and morbidity after breast irradiation using contemporary irradiation techniques. METHODS: The medical records of 961 consecutive patients presenting between 1977 and 1994 with stage I or II breast cancer treated with breast conservation treatment were reviewed. Data was recorded on baseline pretreatment patient, tumor and treatment characteristics and on subsequent cancer or cardiac related events. The median follow-up time was 12 years. RESULTS: There was no difference in overall mortality from any cardiac cause (P = .25). Death from any cardiac cause occurred in 2% of right-sided patients and 3.5% of left-sided patients. However, in the second decade after treatment, there was a higher rate of cardiac deaths in left-sided patients, with a cumulative risk of 6.4% (95% CI, 3.5% to 11.5%) for left-sided compared with 3.6% (95% CI, 1.8% to 7.2%) for right-sided patients at 20 years. There were statistically higher rates of chest pain, coronary artery disease, and myocardial infarction diagnosed in left-sided patients (all P < or = .002). The presence of hypertension was associated with a higher risk of coronary artery disease in left-sided patients. CONCLUSION: Irradiation to the left breast is not associated with a higher risk of cardiac death up to 20 years after treatment, but is associated with an increased rate of diagnoses of coronary artery disease and myocardial infarction compared with right breast treatment.

Adult↗

Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer.

PURPOSE: We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. METHODS: A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. RESULTS: There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). CONCLUSION: IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.

Adult↗

Choice of beam energy and dosimetric implications for radiation treatment in a subpopulation of women with large breasts in the United States and Japan.

Radiation complications are often related to the dose inhomogeneity (hot spot) in breast tissue treated with conservative therapy, especially for large patients. The effect of photon energy on radiation dose distribution is analyzed to provide guidelines for the selection of beam energy when tangential fields and limited slices are used to treat women with large breasts. Forty-eight patients with chest wall separation > 22 cm were selected for dosimetric analysis. We compared the maximum dose in the central axis (CAX) plane (2D) using 6-, 10-, and 18-MV photon beams in all patients and 3D data set for 16 patients. Correlation between hot spot dose (HSD), separation, breast cup size, breast volume, and body weight was derived with beam energy. Among the 48 patients in this study, HSD > 10% in the CAX plane was noted in 98%, 46%, and 4% of the population when 2D dosimetry was performed; however, with 3D study, it was in 50%, 19%, and 6% of the patients with 6-MV, 10-MV and 18-MV beams, respectively. The chest wall separation, body weight, and breast volume were correlated with the HSD in both the 2D and 3D plans. Patient's bra size was not correlated with the hot spot. The chest wall separation was found to be the most important parameter to correlate with hot spot in tangential breast treatment. Simple guidelines are provided for dose uniformity in breast with respect to chest wall separation, body weight, bra size, and breast volume with tangential field irradiations.

Body Weight↗

Similar long-term results of breast-conservation treatment for Stage I and II invasive lobular carcinoma compared with invasive ductal carcinoma of the breast: The University of Pennsylvania experience.

BACKGROUND: The objective of the current study was to determine the long-term results of breast-conservation treatment in women with early-stage, invasive lobular carcinoma of the breast. METHODS: Between 1977 and 1995, 1093 women with Stage I and II invasive ductal carcinoma of the breast and 55 women with invasive lobular carcinoma of the breast underwent lumpectomy, axillary lymph node dissection, and radiation treatment. Overall, 49% of the women received adjuvant systemic therapy (chemotherapy and/or hormones). RESULTS: The median age was 52 years for patients in the invasive ductal group and 54 years for patients in the invasive lobular group. The median follow-up was 8.7 years and 10.2 years for patients in the invasive ductal and invasive lobular groups, respectively. A comparison of patients who had invasive lobular carcinoma with patients who had invasive ductal carcinoma showed no difference in the 10-year actuarial rates of overall survival (85% vs. 79%, respectively; P = 0.73), cause-specific survival (93% vs. 84%, respectively; P = 0.85), or freedom from distant metastases (81% vs. 80%, respectively; P = 0.76). The 10-year rates of local failure were 18% for patients with invasive lobular carcinoma and 12% for patients with invasive ductal carcinoma (P = 0.24), and the 10-year rates of contralateral breast carcinoma development for the 2 groups were 12% and 8%, respectively (P = 0.40). CONCLUSIONS: Breast-conservation treatment yielded similar long-term results for women with early-stage, invasive lobular carcinoma and women with the more prevalent invasive ductal carcinoma.

Adult↗

Analysis of interfraction and intrafraction variation during tangential breast irradiation with an electronic portal imaging device.

PURPOSE: To evaluate the daily setup variation and the anatomic movement of the heart and lungs during breast irradiation with tangential photon beams, as measured with an electronic portal imaging device. METHODS AND MATERIALS: Analysis of 1,709 portal images determined changes in the radiation field during a treatment course in 8 patients. Values obtained for every image included central lung distance (CLD) and area of lung and heart within the irradiated field. The data from these measurements were used to evaluate variation from setup between treatment days and motion due to respiration and/or patient movement during treatment delivery. RESULTS: The effect of respiratory motion and movement during treatment was minimal: the maximum range in CLD for any patient on any day was 0.25 cm. The variation caused by day-to-day setup variation was greater, with CLD values for patients ranging from 0.59 cm to 2.94 cm. Similar findings were found for heart and lung areas. CONCLUSIONS: There is very little change in CLD and corresponding lung and heart area during individual radiation treatment fractions in breast tangential fields, compared with a relatively greater amount of variation that occurs between days.

Adult↗

Long-term outcome after breast-conservation treatment with radiation for mammographically detected ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) is detected most commonly on routine screening mammography in the asymptomatic patient, and has a long natural history. The objective of the current study was to determine the long-term outcome after breast-conservation surgery followed by definitive breast irradiation for women with mammographically detected DCIS of the breast. METHODS: In total, 1003 women with unilateral, mammographically detected DCIS of the breast underwent breast-conserving surgery followed by definitive breast irradiation. These women were treated in 10 institutions in North America and Europe. The median follow-up was 8.5 years (mean, 9.0 years; range, 0.2-24.6 years). RESULTS: The 15-year overall survival rate was 89%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 97%. In total, there were 100 local failures (10%) in the treated breast. The 15-year rate of any local failure was 19%, and the 15-year rate of local only first failure was 16%. Patient age > or = 50 years at the time of treatment and negative final pathology margins from the primary tumor excision both were associated independently with a lower risk of local failure in univariate analysis (P = 0.00062 and P = 0.024, respectively) and in multivariate analysis (P = 0.00057 and P = 0.0026, respectively). For favorable subgroups of patients age > or = 50 years or with negative resection margins, the 10-year risk of local failure was < or = 8%. CONCLUSIONS: The current results support the use of breast-conserving surgery followed by definitive breast irradiation for the treatment of patients with mammographically detected DCIS of the breast. Patient age > or = 50 years at the time of treatment and negative resection margins both were associated independently with a decreased risk of local failure.

Adult↗

Skin-sparing mastectomy and immediate reconstruction is an acceptable treatment option for patients with high-risk breast carcinoma.

BACKGROUND: Skin-sparing mastectomy (SSM) followed by immediate reconstruction is an effective treatment option for patients with early-stage breast carcinoma, but its use in patients with more advanced disease is controversial. METHODS: A retrospective review was performed that included 38 consecutive patients with high-risk breast carcinoma who underwent SSM and immediate reconstruction (between July 1996 and January 2002). Tumor characteristics, type of reconstruction, margin status, timing of adjuvant therapy, postoperative complications, and incidence of recurrence were evaluated. RESULTS: High-risk patients (Stage IIA [n=4 patients] Stage IIB [n=23 patients] Stage IIIA [n=8 patients] and Stage IIIB [n=3 patients]) underwent immediate reconstruction after SSM with the use of a transverse rectus abdominis myocutaneous flap (n=31 patients), a latissimus dorsi myocutaneous flap plus an implant (n=3 patients), or tissue expanders with subsequent implant placement (n=4 patients). The median follow-up was 52.9 months (range, 27.5-92.0 months), and the median time to recurrence has not yet been reached at the time of last follow-up. The median interval from surgery to the initiation of postoperative adjuvant therapy was 38 days (range, 25-238 days). Local recurrence was seen in 1 patient (2.6%), systemic recurrence in was seen in 10 patients (26.3%), and both local and distant metastases in were seen in 2 other patients (5.3%). CONCLUSIONS: SSM with immediate reconstruction appeared to be an oncologically safe treatment option for high-risk patients with advanced stages of breast carcinoma. In addition to the aesthetic and psychological benefits of performing SSM with immediate reconstruction, local recurrence rates and disease-free survival were favorable when combined with the use of radiation therapy and adjuvant chemotherapy, as indicated.

Adult↗

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ.

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.

Adult↗

Paget's disease of the nipple as local recurrence after breast-conservation treatment for early-stage breast cancer.

Breast conservation treatment (BCT) for early-stage breast cancer is associated with survival rates comparable with mastectomy but has the risk of ipsilateral breast tumor recurrence, including Paget's disease of the nipple. A small number of cases of Paget's disease presenting as local recurrence following BCT for breast cancer have been previously reported. Between 1977 and 2002, 2181 women with early-stage breast cancer were treated with BCT at the Hospital of the University of Pennsylvania. In this cohort, there were 183 local treatment failures, 4 of which were cases of Paget's disease (2.2%), which are reported herein. These local recurrences developed 1.8, 3.8, 7.3, and 9.7 years after diagnosis of the patients' primary tumors. Three of the 4 primary cancers were invasive ductal carcinomas, with an associated intraductal component, and 1 was ductal carcinoma in situ. All 4 patients were successfully given salvage therapy consisting of mastectomy with or without tamoxifen, with follow-up times of 20.9, 10.6, 3.1, and 3.8 years. Paget's disease as local recurrence after BCT is uncommon and can be treated with salvage therapy if detected early.

Aged↗

Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment.

PURPOSE: To assess the impact of sequencing of tamoxifen and radiation therapy (RT) on outcomes in early-stage breast cancer. PATIENTS AND METHODS: This retrospective study evaluates the effect of the sequence of tamoxifen with RT on outcomes in stage I to II breast cancer patients who underwent breast-conservation treatment (BCT) and received adjuvant tamoxifen, with or without adjuvant chemotherapy. Patients were grouped as concurrent (tamoxifen given during RT followed by continued tamoxifen; 174 patients) and sequential (RT followed by tamoxifen; 104 patients). RESULTS: Median follow-up after RT was 8.6 years for both groups. The pathologic T and N stage, race, estrogen and progesterone status, number of positive nodes, and RT were comparable between the two groups (all P >/= .08). More women age 49 years or younger and women who received chemotherapy were in the sequential group than the concurrent group (6% and 25%, respectively; P < .0001). The sequence of tamoxifen therapy did not influence 10-year local recurrence rates (sequential, 7%; concurrent, 3%; P = .52), overall survival (sequential, 86%; concurrent, 81%; P = .64), or relapse-free survival (sequential, 76%; concurrent, 85%; P = .35). When adjusting age and chemotherapy use in the multivariable Cox model, hazard ratios comparing sequential versus concurrent tamoxifen therapy were 1.56 (95% CI, 0.87 to 2.79), 1.23 (95% CI, 0.63 to 2.41), and 1.22 (95% CI, 0.33 to 4.49) for the overall survival, relapse-free survival, and local recurrence, respectively. CONCLUSION: The therapeutic regimens of tamoxifen given concurrently or sequentially with RT both appear to be reasonable options for patients treated with BCT.

Adult↗

Efficacy of radiotherapy for ovarian ablation: results of a breast intergroup study.

BACKGROUND: In 1994, the Eastern Cooperative Oncology Group (ECOG) initiated for the Breast Intergroup a randomized clinical trial (E3193) in premenopausal patients with early-stage breast carcinoma (lymph node-negative and receptor-positive, with tumors measuring < or = 3 cm) comparing tamoxifen as adjuvant systemic therapy with tamoxifen and ovarian ablation by one of three different methods. Ovarian ablation could be accomplished either via radiotherapy (RT) (20 Gray [Gy]/10 fractions to a modified pelvic volume), surgical oophorectomy, or goserelin/leuprolide injections as per patient/physician choice. In the current study, we report the efficacy of pelvic RT with this dose-fractionation scheme in the induction of ovarian ablation. METHODS: Twenty-two of 174 patients (13%) who were randomized to treatment with tamoxifen and ovarian ablation received RT for ovarian ablation. RT quality assurance was performed. Of the 22 patients, 19 were treated per protocol, 1 patient had a minor violation (20 elapsed days for 10 RT fractions), and 2 patients had major violations (1 patient who was treated with RT as per protocol but who was treated at a non-Intergroup center, and 1 patient who was treated at a dose of 15 Gy/5 fractions). RESULTS: No acute Grade 3 or 4 (according to the Common Toxicity Criteria of the National Cancer Institute) toxicities were reported during RT. Of the 22 patients receiving RT, evaluable follow-up data were available for 20 patients. Based on postmenopausal levels of estradiol or follicle-stimulating hormone at varying intervals after the completion of RT, 15 of 20 patients (75%) achieved successful ovarian ablation with RT. At a median follow-up of 54 months (range, 21-66 months), no Grade 3 or 4 complications from RT were observed. CONCLUSIONS: Ovarian ablation by RT as performed in the current trial (given at a dose of 20 Gy in 10 fractions to a modified pelvic treatment volume) was found to be effective for ovarian ablation in the majority of patients, but may take some months to be complete. Consequently, patients should be evaluated to ascertain that ablation has been accomplished.

Adult↗

Fifteen-year results of breast-conserving surgery and definitive irradiation for Stage I and II breast carcinoma: the University of Pennsylvania experience.

PURPOSE: To determine the 15-year outcomes for women with early stage breast cancer after breast conservation therapy. METHODS AND MATERIALS: Between 1977 and 1990, 937 women with Stage I and II breast carcinoma (55% T1N0, 16% T2N0, 18% T1N1, and 11% T2N1) underwent lumpectomy, axillary lymphadenectomy, and definitive irradiation. The median patient age was 52 years. Of the 937 patients, 375 (40%) received adjuvant chemotherapy and/or hormonal therapy, including 249 (92%) of the 270 women with pathologically positive nodes. The median follow-up was 10.1 years. RESULTS: For the overall group, the 15-year overall survival rate was 71%, and the rate of freedom from distant metastases was 76%. The 15-year local failure rate was 19%. The 15-year contralateral breast cancer rate was 12%. The most common first events were distant failure (13%), local failure (10%), contralateral breast cancer (7%), and second malignant neoplasms (6%). The local failure rate at 10 years for favorable subsets of tumors characterized by mammographic detection, resection with negative margins, treatment with chemotherapy, and treatment with hormones was 8%, 10%, 10%, and 7%, respectively. Local failures were most commonly observed within (true recurrence), or just outside (marginal miss), the primary tumor bed (66%, 85 of 128). The rate of true recurrence or marginal miss at 5, 10, and 15 years was 5%, 10%, and 12%, respectively. CONCLUSION: These high rates of survival and local control confirm that breast conservation therapy yields favorable results in women with early breast cancer into the second decade after treatment.

Adult↗