Complications After Total Skin-Sparing Mastectomy and Expander-Implant Reconstruction: Effects of Radiation Therapy on the Stages of Reconstruction.

BACKGROUND: Many patients undergoing total-skin sparing mastectomy (TSSM) and 2-staged expander-implant (TE-I) reconstruction require postmastectomy radiation therapy (PMRT). Additionally, many patients undergoing TSSM for recurrent cancer have a history of lumpectomy and radiation therapy (XRT). Few studies have looked at the impact of XRT on the stages of TE-I reconstruction. METHODS: Patients undergoing TSSM and immediate TE-I reconstruction between 2006 and 2013 were identified from a prospectively maintained database. Rates of TE-I loss and severe infection requiring intravenous antibiotics were compared in patients with prior XRT (85 cases) and PMRT (133 cases). Complications were divided by stage of reconstruction: first stage (TSSM and TE placement) and second stage (TE-I exchange). RESULTS: Mean follow-up time was 2.5 years. Patients with prior XRT had more complications after the first stage of reconstruction than the second (TE-I loss: 15% vs 5%, P = 0.03; infection: 20% vs 8%, P = 0.04). Patients receiving PMRT had low complication rates after the first stage, when they had not yet received radiation (TE-I loss: 2%; infection: 5%). However, complication rates after TE-I exchange (TE-I loss, 18%; infection, 31%) were significantly higher, and nearly 4-fold higher than patients with prior XRT. CONCLUSIONS: Patients with prior XRT are at high risk for complications after the first stage of TE-I reconstruction after TSSM; however, the risk of complications at the second stage is comparable to patients without radiation exposure and significantly lower than patients receiving PMRT. Patients receiving radiation therapy should be given appropriate preoperative counseling regarding their risks.

Sentinel Lymph Node Mapping in Post-Mastectomy Chest Wall Recurrences: Influence on Radiation Treatment Fields and Outcome.

BACKGROUND AND OBJECTIVES: Invasive chest wall recurrences (CWR) following mastectomy are typically treated with surgical excision, radiation therapy (RT) to the chest wall and supraclavicular (SCV) region, and appropriate systemic therapy. Repeat axillary surgery is not routinely performed if the axilla is clinically negative. We evaluated sentinel node biopsy (SNB) in patients with an isolated invasive CWR, for identification and biopsy rates, non-axillary drainage, and clinical implications for radiation fields and outcome. METHODS: Between 2008 and 2013, 12/19 women with an isolated invasive CWR had sentinel node (SN) mapping with Tc99m. Median age was 53 years, and 92% (11/12) had initial path N0 disease. All had prior SNB, with axillary dissection in one patient. RESULTS: Overall, 83% (10/12) had successful mapping, with 70% (7/10) having an axillary SN. Ninety percent (9/10) had successful axillary node biopsy, with one patient having positive nodes. SCV RT was omitted in those with negative axillary nodes. With a median follow-up of 4.6 years from recurrence, there have been no SCV recurrences and no instances of lymphedema. CONCLUSIONS: SNB is possible in women with an isolated CWR with acceptable identification and biopsy rates. Omission of routine irradiation of the SCV region has not jeopardized regional control and results in decreased morbidity.

Risk of positive nonsentinel nodes in women with 1-2 positive sentinel nodes related to age and molecular subtype approximated by receptor status.

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1-2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1-2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1-10) and 14 (range 6-37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.

Survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status.

BACKGROUND: Randomized clinical trials (RCT) have demonstrated equivalent survival for breast-conserving therapy with radiation (BCT) and mastectomy for early-stage breast cancer. A large, population-based series of women who underwent BCT or mastectomy was studied to observe whether outcomes of RCT were achieved in the general population, and whether survival differed by surgery type when stratified by age and hormone receptor (HR) status. METHODS: Information was obtained regarding all women diagnosed in the state of California with stage I or II breast cancer between 1990 and 2004, who were treated with either BCT or mastectomy and followed for vital status through December 2009. Cox proportional hazards modeling was used to compare overall survival (OS) and disease-specific survival (DSS) between BCT and mastectomy groups. Analyses were stratified by age group (< 50 years and ≥ 50 years) and tumor HR status. RESULTS: A total of 112,154 women fulfilled eligibility criteria. Women undergoing BCT had improved OS and DSS compared with women with mastectomy (adjusted hazard ratio for OS entire cohort = 0.81, 95% confidence interval [CI] = 0.80-0.83). The DSS benefit with BCT compared with mastectomy was greater among women age ≥ 50 with HR-positive disease (hazard ratio = 0.86, 95% CI = 0.82-0.91) than among women age < 50 with HR-negative disease (hazard ratio = 0.88, 95% CI = 0.79-0.98); however, this trend was seen among all subgroups analyzed. CONCLUSIONS: Among patients with early stage breast cancer, BCT was associated with improved DSS. These data provide confidence that BCT remains an effective alternative to mastectomy for early stage disease regardless of age or HR status.

Radiotherapy Utilization for Patients Over Age 60 With Early Stage Breast Cancer.

INTRODUCTION: Recent studies have questioned the relative benefit of radiotherapy (RT) for older patients with favorable breast cancer given the lack of survival benefit and marginal local control benefit. Despite the 2004 National Comprehensive Cancer Network (NCCN) guidelines advocating for the option of hormonal therapy alone, trends in utilization rates of RT in this group are not well-documented. We analyzed our institutional experience with implementation of the guidelines over time. MATERIAL AND METHODS: We identified 564 patients aged ≥ 60 years with favorable breast cancer treated with breast conserving surgery from 2000 to 2017. Patients met criteria for Cancer and Leukemia Group B (CALGB) 9343, Postoperative Radiotherapy in Minimum Risk Elderly (PRIME II), or the very-low risk cohort identified in the Toronto-British Columbia study. Multivariable logistic regression analysis was performed to assess the magnitude of association between omission status, grade, and tumor size while controlling for age and year of diagnosis. RESULTS: Overall RT omission rates were 17.6% prior to the 2004 NCCN update and 45% after the publication of the 10-year CALGB data in 2013. The overall RT omission rate was 29%. Patients with grade 1 to 2 histology (odds ratio, 3.2; 95% confidence interval, 1.3-7.7; P = .01) and tumors < 1 cm (odds ratio, 1.60; 95% confidence interval, 0.4-0.9; P = .007) were more likely to omit RT than those with higher grade or larger tumors. CONCLUSIONS: We observed a slight decrease in the use of RT over time, suggesting a move towards adoption of the NCCN guidelines. There remains a fundamental need to continue to individualize breast cancer care based on risk stratification and make evidenced-based treatment recommendations with equitable use of health care resources.

Indications for Postmastectomy Radiation After Neoadjuvant Chemotherapy in ypN0 and ypN1-3 Axillary Node-Positive Women.

INTRODUCTION: Downstaging with neoadjuvant chemotherapy (NAC) might obscure indications for postmastectomy radiation (PMRT). The degree of downstaging that results in local-regional recurrence (LRR) rates low enough to omit PMRT remains controversial. We examined the rate of LRR in women who received NAC who underwent mastectomy without PMRT. PATIENTS AND METHODS: Between 2004 and 2013, 81 women with stage I to IIIA breast cancer had NAC and mastectomy; 48 patients (59%) were clinical N0 and 33 patients (41%) were clinical N1; median age was 45 years; 33 patients (41%) had hormone receptor-positive (HR+)HER2-, 21 patients (26%) HR+HER2+, 19 patients (23%) HR- HER2-, and 7 patients (9%) HR-HER2+ disease. We explored how LRR rates varied with age, BRCA status, Grade, receptor status, clinical N status, pathologic response, lymphovascular invasion, and mastectomy margins. Median follow-up was 4.9 years. RESULTS: After NAC, 35 patients (43%) had a pathologic complete response (pCR), 33 patients (41%) were ypN0, and 13 patients (16%) were ypN1-3+. There were 8 LRRs (6 chest wall, 1 axillary, 1 supraclavicular node). The 5-year cumulative incidence of LRR was 8% for all patients, 3% for pCR, 16% for ypN0, 10% for ypN1-3+, 6% for HR+HER2-, 25% for HR+HER2+, 0% for HR-HER2-, and 0% for HR-HER2+. LRR was 31% in the ypN0 and 33% in the ypN1-3+ HR+HER2+ women, and 12% in the ypN0 and 0% in the ypN1 to ypN3+ HR+HER2- patients. CONCLUSION: This study is unique. All HER2+ patients received trastuzumab and LRR was analyzed according to treatment response, clinicopathologic factors, and receptor status. pCR patients including young women and clinical stage IIIA had low LRR rates. However, ypN0 and ypN1-3+ HR+HER2+ patients had higher rates of LRR compared with other receptor subgroups and on the basis of limited data should be considered for PMRT.

An Innovative Risk-Reducing Approach to Postmastectomy Radiation Delivery after Autologous Breast Reconstruction.

INTRODUCTION: Postmastectomy radiation therapy (PMRT) has known deleterious side effects in immediate autologous breast reconstruction. However, plastic surgeons are rarely involved in PMRT planning. Our institution has adopted a custom bolus approach for all patients receiving PMRT. This offers uniform distribution of standard radiation doses, thereby minimizing radiation-induced changes while maintaining oncologic safety. We present our 8-year experience with the custom bolus approach for PMRT delivery in immediate autologous breast reconstruction. METHODS: All immediate autologous breast reconstruction patients requiring PMRT after 2006 were treated with the custom bolus approach. Retrospective chart review was performed to compare the postirradiation complications, reconstruction outcomes, and oncologic outcomes of these patients with those of previous patients at our institution who underwent standard bolus, and to historical controls from peer-reviewed literature. RESULTS: Over the past 10 years, of the 29 patients who received PMRT, 10 were treated with custom bolus. Custom bolus resulted in fewer radiation-induced skin changes and less skin tethering/fibrosis than standard bolus (0% vs 10% and 20% vs 35%, respectively), and less volume loss and contour deformities compared with historical controls (10% vs 22.8% and 10% vs 30.7%, respectively). CONCLUSIONS: Custom bolus PMRT minimizes radiation delivery to the internal mammary vessels, anastomoses, and skin; uniformly doses the surgical incision; and provides the necessary radiation dose to prevent recurrence. Because custom bolus PMRT may reduce the deleterious effects of radiation on reconstructive outcomes while maintaining safe oncologic results, we encourage all plastic surgeons to collaborate with radiation oncologists to consider this technique.

Evaluation of Heart Dose for Left-Sided Breast Cancer Patients Over an 11-Year Period Spanning the Transition From 2-Dimensional to 3-Dimensional Planning.

INTRODUCTION/BACKGROUND: We evaluated heart dose from left breast radiotherapy with 2-dimensional (2D) versus 3-dimensional (3D) plans. PATIENTS AND METHODS: Treatment plans from patients treated with standard fractionation for left breast cancer from 2003 to 2013 were reviewed, with patients grouped into 3 cohorts: 2003 to 2004 ("2D", with computed tomography scans for dose calculation but fields defined using simulation films; n = 29), 2005 to 2006 ("2D-post," after several influential articles on heart dose were published; n = 31), and 2007 to 2013 ("3D"; n = 256). All patients were treated with free-breathing technique. Heart volumes were retrospectively contoured for the earlier 2 cohorts. Mean heart dose (MHD) and percentage of structure receiving at least 25 Gy (V25 Gy) and percentage of structure receiving at least 5 Gy for the whole heart, left ventricle (LV), right ventricle (RV), and both ventricles were recorded and compared among cohorts. RESULTS: MHD was 345 cGy (2D), 213 cGy (2D-post) and 213 cGy (3D). LV V25 Gy was 6.3%, 1.5%, and 1.1%, respectively. Lower doses were seen over time for all indices (analysis of variance, P < .0001). Post hoc tests indicated significantly higher doses for 2D versus 2D-post or 3D cohorts (P ≤ .001) for all parameters except RV V25 Gy (P = .24). CONCLUSION: Heart doses were higher with 2D versus 3D plans. Cardiac doses and resulting toxicity with modern 3D planning might be lower than those in previous reports.

The Impact of Radiation Therapy, Lymph Node Dissection, and Hormonal Therapy on Outcomes of Tissue Expander-Implant Exchange in Prosthetic Breast Reconstruction.

BACKGROUND: Total skin-sparing mastectomy, with preservation of the nipple-areola complex, must account for adjuvant medical and surgical treatments for cancer. The authors assessed risk factors for complications after second-stage tissue expander-implant exchange. METHODS: The authors reviewed all institutional total skin-sparing mastectomy cases that had completed tissue expander-implant exchange with at least 3 months of follow-up. They developed multivariate generalized estimating equation models to obtain adjusted relative risks of radiation therapy, type of lymph node dissection, and hormonal therapy in relation to postoperative complications. RESULTS: The authors performed 776 cases in 489 patients, with a median follow-up of 26 months (interquartile range, 10 to 48 months). Radiation therapy was associated with increased wound breakdown risk [relative risk (RR), 3.3; 95 percent CI, 2.0 to 5.7]; infections requiring oral antibiotics (RR, 2.2; 95 percent CI, 1.31 to 3.6), intravenous antibiotics (RR, 6.4; 95 percent CI, 3.9 to 10.7), or procedures (RR, 8.9; 95 percent CI, 4.5 to 17.5); implant exposure (RR, 3.9; 95 percent CI, 1.86 to 8.3); and implant loss (RR, 4.2; 95 percent CI, 2.4 to 7.4). Axillary lymph node dissection was associated with an increased risk of implant loss (RR, 2.0; 95 percent CI, 1.11 to 3.7) relative to sentinel lymph node biopsy. CONCLUSIONS: Axillary lymph node dissection increases the risk of implant loss compared with sentinel lymph node biopsy, independent of radiation therapy. Patients who require axillary lymph node dissection may be encouraged to undergo breast conservation or autologous reconstruction when possible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Endocrine Therapy for Hormone Receptor-Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline.

PURPOSE: To develop recommendations about endocrine therapy for women with hormone receptor (HR) -positive metastatic breast cancer (MBC). METHODS: The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of evidence from 2008 through 2015 to create recommendations informed by that evidence. Outcomes of interest included sequencing of hormonal agents, hormonal agents compared with chemotherapy, targeted biologic therapy, and treatment of premenopausal women. This guideline puts forth recommendations for endocrine therapy as treatment for women with HR-positive MBC. RECOMMENDATIONS: Sequential hormone therapy is the preferential treatment for most women with HR-positive MBC. Except in cases of immediately life-threatening disease, hormone therapy, alone or in combination, should be used as initial treatment. Patients whose tumors express any level of hormone receptors should be offered hormone therapy. Treatment recommendations should be based on type of adjuvant treatment, disease-free interval, and organ function. Tumor markers should not be the sole criteria for determining tumor progression; use of additional biomarkers remains experimental. Assessment of menopausal status is critical; ovarian suppression or ablation should be included in premenopausal women. For postmenopausal women, aromatase inhibitors (AIs) are the preferred first-line endocrine therapy, with or without the cyclin-dependent kinase inhibitor palbociclib. As second-line therapy, fulvestrant should be administered at 500 mg with a loading schedule and may be administered with palbociclib. The mammalian target of rapamycin inhibitor everolimus may be administered with exemestane to postmenopausal women with MBC whose disease progresses while receiving nonsteroidal AIs. Among patients with HR-positive, human epidermal growth factor receptor 2-positive MBC, human epidermal growth factor receptor 2-targeted therapy plus an AI can be effective for those who are not chemotherapy candidates.

Rates of Reconstruction Failure in Patients Undergoing Immediate Reconstruction With Tissue Expanders and/or Implants and Postmastectomy Radiation Therapy.

OBJECTIVES: Mastectomy rates for breast cancer have increased, with a parallel increase in immediate reconstruction. For some women, tissue expander and implant (TE/I) reconstruction is the preferred or sole option. This retrospective study examined the rate of TE/I reconstruction failure (ie, removal of the TE or I with the inability to replace it resulting in no final reconstruction or autologous tissue reconstruction) in patients receiving postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: Between 2004 and 2012, 99 women had skin-sparing mastectomies (SSM) or total nipple/areolar skin-sparing mastectomies (TSSM) with immediate TE/I reconstruction and PMRT for pathologic stage II to III breast cancer. Ninety-seven percent had chemotherapy (doxorubicin and taxane-based), 22% underwent targeted therapies, and 78% had endocrine therapy. Radiation consisted of 5000 cGy given in 180 to 200 cGy to the reconstructed breast with or without treatment to the supraclavicular nodes. Median follow-up was 3.8 years. RESULTS: Total TE/I failure was 18% (12% without final reconstruction, 6% converted to autologous reconstruction). In univariate analysis, the strongest predictor of reconstruction failure (RF) was absence of total TE/I coverage (acellular dermal matrix and/or serratus muscle) at the time of radiation. RF occurred in 32.5% of patients without total coverage compared to 9% with coverage (P=.0069). For women with total coverage, the location of the mastectomy scar in the inframammary fold region was associated with higher RF (19% vs 0%, P=.0189). In multivariate analysis, weight was a significant factor for RF, with lower weight associated with a higher RF. Weight appeared to be a surrogate for the interaction of total coverage, thin skin flaps, interval to exchange, and location of the mastectomy scar. CONCLUSIONS: RFs in patients receiving PMRT were lowered with total TE/I coverage at the time of radiation by avoiding inframammary fold incisions and with a preferred interval of 6 months to exchange.

Practice patterns in the delivery of radiation therapy after mastectomy among the University of California Athena Breast Health Network.

BACKGROUND: Practice patterns vary with the planning and delivery of PMRT. In our investigation we examined practice patterns in the use of chest wall bolus and a boost among the Athena Breast Health Network (Athena). MATERIALS AND METHODS: Athena is a collaboration among the 5 University of California Medical Centers that aims to integrate clinical care and research. From February 2011 to June 2011, all physicians specializing in the multidisciplinary treatment of breast cancer were invited to take a Web-based practice patterns survey. Sixty-two of the 239 questions focused on radiation therapy practice environment, decision-making processes, and treatment management, including the use of a bolus or boost in PMRT. RESULTS: Ninety-two percent of the radiation oncologists specializing in breast cancer completed the survey. All of the responders use a material to increase the surface dose to the chest wall during PMRT. Materials used included brass mesh, commercial bolus, and custom-designed wax bolus. Fifty percent used tissue equivalent superflab bolus. Fifty-five percent of the respondents routinely use a boost to the chest wall in PMRT. Eighteen percent give a boost depending on the margin status, and 3 of 11 (27%) do not use a boost. CONCLUSION: Our investigation documents practice pattern variation for the use of a PMRT boost and the use of chest wall bolus among the University of California breast cancer radiation oncologists. Further understanding of the practice pattern variation will help guide clinicians in our cancer centers to a more uniform approach in the delivery of PMRT.

Impact of total skin-sparing mastectomy incision type on reconstructive complications following radiation therapy.

BACKGROUND: Postoperative complications after total skin-sparing mastectomy and expander-implant reconstruction can negatively impact outcomes, particularly in the setting of postmastectomy radiation therapy. The authors studied whether rates of ischemic complications after postmastectomy radiation therapy are impacted by the total skin-sparing mastectomy incision. METHODS: The authors queried a prospectively collected database of patients undergoing total skin-sparing mastectomy and immediate two-stage expander-implant reconstruction. Their hypothesis was that, in the setting of radiation therapy, patients with inframammary incisions would be more likely to develop ischemic complications than those without incisions on the dependent portion of the breast. We divided our patient cohort into two groups, those with inframammary incisions and those with other incisions, and then analyzed the proportion that received radiation therapy. RESULTS: Of 756 cases included in the analysis, 91 (12 percent) received postmastectomy radiation therapy, 62 (68.1 percent) with inframammary incisions and 29 (31.9 percent) with other incisions. Mean follow-up was 3.1 years. Rates of mastectomy skin flap necrosis (3.2 percent versus 6.9 percent, p=0.4) following radiation therapy were not significantly higher in the inframammary group. However, breakdown of the total skin-sparing mastectomy incision was twice as likely in the inframammary group (21 percent versus 10.3 percent, p=0.2) and was more likely to lead to subsequent implant removal when incisional breakdown occurred (77 percent versus 0 percent, p=0.03). CONCLUSIONS: Total skin-sparing mastectomy incision type may impact rates of incisional breakdown and implant loss following postmastectomy radiation therapy, with higher rates seen with inframammary incisions. Multiple factors, including breast size, breast ptosis, and likelihood of radiation therapy, should be considered in determining optimal incision. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Immediate implant-based breast reconstruction following total skin-sparing mastectomy: defining the risk of preoperative and postoperative radiation therapy for surgical outcomes.

BACKGROUND: Radiation therapy is increasingly used in breast cancer therapy. With total skin-sparing mastectomy and nipple/areola complex preservation, defining the risks of various treatment regimens for morbidity is important, in the setting of immediate prosthetic reconstruction. The authors assessed the effects of premastectomy and postmastectomy radiation therapy on outcomes in total skin-sparing mastectomy and immediate prosthetic reconstruction. METHODS: All patients undergoing total skin-sparing mastectomy and immediate prosthetic reconstruction at the authors' institution between 2006 and 2012 were identified. Cohort 1 included patients undergoing total skin-sparing mastectomy and reconstruction with no radiation. Cohort 2 included patients with a prior history of radiation before total skin-sparing mastectomy and reconstruction. Cohort 3 included patients undergoing radiation after total skin-sparing mastectomy and reconstruction. RESULTS: A total of 580 patients underwent 903 breast reconstructions following total skin-sparing mastectomy. Cohort 1 included 727 breasts, cohort 2 included 63 breasts, and cohort 3 included 113 breasts. Any radiation delivery caused an increased rate of infection requiring antibiotics (21.6 percent, p = 0.00) and an increased risk of expander/implant loss (18.75 percent, p = 0.00). Cohort 2 had a higher risk of wound breakdown (p = 0.012). All cohorts showed similar low rates of nipple/areola necrosis. CONCLUSIONS: Both preoperative and postoperative radiation following total skin-sparing mastectomy and immediate prosthetic reconstruction result in higher, but acceptable, complication risks. Complications related to nipple/areola preservation are similar to those in nonradiated patients and in those undergoing skin-sparing mastectomy. Thus, nipple/areola complex preservation is safe in women undergoing radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Effect of Bra Use during Radiotherapy for Large-Breasted Women: Acute Toxicity and Treated Heart and Lung Volumes.

PURPOSE: Large breast size presents special problems during radiation simulation, planning and patient treatment, including increased skin toxicity, in women undergoing breast-conserving surgery and radiotherapy (BCT). We report our experience using a bra during radiation in large-breasted women and its effect on acute toxicity and heart and lung dosimetry. MATERIALS AND METHODS: From 2001 to 2006, 246 consecutive large-breasted women (bra size ≥ 38 and/or ≥ D cup) were treated with BCT using either 3D conformal (3D-CRT) or Intensity Modulated Radiation (IMRT). In 58 cases, at the physicians' discretion, a custom-fit bra was used during simulation and treatment. Endpoints were acute radiation dermatitis, and dosimetric comparison of heart and lung volumes in a subgroup of 12 left-sided breast cancer patients planned with and without a bra. RESULTS: The majority of acute skin toxicities were grade 2 and were experienced by 90% of patients in a bra compared to 70% of patients not in a bra (p=0.003). On multivariate analysis significant predictors of grade 2/3 skin toxicity included 3D-CRT instead of IMRT (OR=3.9, 95% CI:1.8-8.5) and the use of a bra (OR=5.5, 95% CI:1.6-18.8). For left-sided patients, use of a bra was associated with a volume of heart in the treatment fields decreased by 63.4% (p=0.002), a volume of left lung decreased by 18.5% (p=0.25), and chest wall separation decreased by a mean of 1 cm (p=0.03). CONCLUSIONS: The use of a bra to augment breast shape and position in large-breasted women is an alternative to prone positioning and associated with reduced chest wall separation and reduced heart volume within the treatment field.

Effect of bra use during radiation therapy for large-breasted women: Acute toxicity and treated heart and lung volumes.

PURPOSE: Large breast size presents special problems during radiation simulation, planning, and patient treatment, including increased skin toxicity, in women undergoing breast-conserving surgery and radiation therapy (BCT). We report our experience using a bra during radiation in large-breasted women and its effect on acute toxicity and heart and lung dosimetry. METHODS AND MATERIALS: From 2001 to 2006, 246 consecutive large-breasted women (bra size ≥38 or ≥D cup) were treated with BCT using either 3-dimensional conformal radiation therapy (3DCRT) or intensity modulated radiation therapy (IMRT). In 58 cases, at the physicians' discretion, a custom-fit bra was used during simulation and treatment. Endpoints were acute radiation dermatitis and dosimetric comparison of heart and lung volumes in a subgroup of 12 left-sided breast cancer patients planned with and without a bra. RESULTS: The majority of acute skin toxicities were grade 2 and were experienced by 90% of patients in a bra compared with 70% of patients not in a bra (P = .003). On multivariate analysis significant predictors of grade 2 or 3 skin toxicity included the use of 3DCRT instead of IMRT (odds ratio, 3.9; 95% confidence interval, 1.8-8.5) and the use of a bra (odds ratio, 5.5; 95% confidence interval, 1.6-18.8). For left-sided patients, the use of a bra was associated with a volume of heart in the treatment fields decreased by 63.4% (P = .002), a volume of left lung decreased by 18.5% (P = .25), and chest wall separation decreased by a mean of 1 cm (P = .03). CONCLUSIONS: The use of a bra to augment breast shape and position in large-breasted women is an alternative to prone positioning and associated with reduced chest wall separation and reduced heart volume within the treatment field.

Increasing the time to expander-implant exchange after postmastectomy radiation therapy reduces expander-implant failure.

BACKGROUND: Increased rates of complications can occur when postmastectomy radiation therapy is required after immediate expander-implant breast reconstruction. The sequence and timing of tissue expansion and implant exchange with regard to postmastectomy radiation therapy may impact complication rates. METHODS: A prospectively maintained database of patients undergoing mastectomy and immediate reconstruction was queried for patients who underwent postmastectomy radiation therapy. The authors' protocol is to complete tissue expansion before radiation, irradiate the fully inflated expander, and then perform expander-implant exchange. Starting in 2009, the authors refined their protocol by increasing the time interval between completion of radiation therapy and expander-implant exchange from 3 months to 6 months as a strategy to reduce surgical complications. For analysis, patients were divided into two cohorts based on whether expander-implant exchange was performed less than 6 months or more than 6 months after radiation. The primary outcome was expander-implant failure, defined as device removal without concurrent replacement. RESULTS: Eighty-eight patients met selection criteria; 49 (55.7 percent) had expander-implant exchange within 6 months of completing radiation therapy (mean, 3.4 months; range, 1.2 to 5.8 months), and the rest had at least a 6-month interval (mean, 8.6 months; range, 6.1 to 17.1 months). Risk factors for postoperative complications were equivalent between cohorts. Overall expander-implant failure was 15.9 percent; failure was significantly higher in the cohort with less than 6 months' time before exchange (22.4 percent versus 7.7 percent, p = 0.036). CONCLUSION: Delaying expander-implant exchange for at least 6 months after the completion of postmastectomy radiation therapy can significantly reduce expander-implant failure.

Role of postmastectomy radiation after neoadjuvant chemotherapy in stage II-III breast cancer.

PURPOSE: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). METHODS AND MATERIALS: Seven breast cancer physicians from the University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. RESULTS: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having ≤ 10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. CONCLUSIONS: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within the University of California Athena Breast Health Network.

Is radiation indicated in patients with ductal carcinoma in situ and close or positive mastectomy margins?

PURPOSE: Resection margin status is one of the most significant factors for local recurrence in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery with or without radiation. However, its impact on chest wall recurrence in patients treated with mastectomy is unknown. The purpose of this study was to determine chest wall recurrence rates in women with DCIS and close (<5 mm) or positive mastectomy margins in order to evaluate the potential role of radiation therapy. METHODS AND MATERIALS: Between 1985 and 2005, 193 women underwent mastectomy for DCIS. Fifty-five patients had a close final margin, and 4 patients had a positive final margin. Axillary surgery was performed in 17 patients. Median follow-up was 8 years. Formal pathology review was conducted to measure and verify margin status. Nuclear grade, architectural pattern, and presence or absence of necrosis was recorded. RESULTS: Median pathologic size of the DCIS in the mastectomy specimen was 4.5 cm. Twenty-two patients had DCIS of >5 cm or diffuse disease. Median width of the close final margin was 2 mm. Nineteen patients had margins of <1 mm. One of these 59 patients experienced a chest wall recurrence with regional adenopathy, followed by distant metastases 2 years following skin-sparing mastectomy. The DCIS was high-grade, 4 cm, with a 5-mm deep margin. A second patient developed an invasive cancer in the chest wall 20 years after her mastectomy for DCIS. This cancer was considered a new primary site arising in residual breast tissue. CONCLUSIONS: The risk of chest wall recurrence in this series of patients is 1.7% for all patients and 3.3% for high-grade DCIS. One out of 20 (5%) patients undergoing skin sparing or total skin-sparing mastectomy experienced a chest wall recurrence. This risk of a chest wall recurrence appears sufficiently low not to warrant a recommendation for postmastectomy radiation therapy for patients with margins of <5 mm. There were too few patients with positive margins to draw any firm conclusions.