Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

Long-Term Clinical and Cosmetic Outcomes of Once-Daily Accelerated Partial Breast Irradiation in Early Breast Cancer.

Purpose: Accelerated partial breast irradiation (APBI) is one of the standard treatment options in early-stage node negative breast cancer in selected patients. However, the optimal dose fractionation schedule still represents a challenge. We present the 12-year follow up results of clinical and cosmetic outcomes of once daily APBI with external beam radiation therapy which provides an APBI radiation dose equivalent to the whole breast radiation with a boost. Methods and Materials: From July 2008 to August 2010, we enrolled 34 patients with T1, T2 (< 3cm) N0 to receive once daily APBI with three dimensional conformal radiation therapy (3D-CRT) to a total dose of 49.95 Gy over 15 single daily fractions over 3 weeks at 3.33 Gy per fraction. Ipsilateral breast tumor recurrence (IBTR), acute toxicity, late toxicity and cosmesis was analyzed. The median follow-up for all patients is 144 months (12 years). Results: The median age of the patients was 61 years (range 46-83). Nine patients had ductal carcinoma in situ (DCIS) and 25 patients had invasive cancer. The median size of the tumor with DCIS pathology was 0.5 cm, while median size of the tumor with invasive cancer pathology was 1.0 cm. All of the patients had negative margins and negative nodes. Two IBTR was observed (5.8%). One patient had DCIS at recurrence and other had invasive recurrence. Two patients died due to non-cancer cause. The 12-year actuarial ipsilateral breast recurrence free survival was 93.5% and the 12-year actuarial overall survival was 93.2%. Late Grade 2 toxicity was observed in 6 patients and late grade 3 toxicity was seen in 1 patient. 91% of the patients had excellent to good cosmesis. Conclusions: This novel APBI dosing schema is based on an equivalent dose compared to whole breast radiation plus a tumor bed boost. This once daily APBI scheme is well-tolerated and demonstrates good to excellent cosmetic outcome and low rates of late complications on long term follow-up.

Clinical efficacy of PARP inhibitors in breast cancer.

BRCA1 and BRCA2 are key tumor suppressor genes that are essential for the homologous recombination DNA repair pathway. Loss of function mutations in these genes result in hereditary breast and ovarian cancer syndromes, which comprise approximately 5% of cases. BRCA1/2 mutations are associated with younger age of diagnosis and increased risk of recurrences. The concept of synthetic lethality led to the development of PARP inhibitors which cause cell cytotoxicity via the inhibition of PARP1, a key DNA repair protein, in cells with germline BRCA1/2 mutations. Although still poorly understood, the most well-acknowledged proposed mechanisms of action of PARP1 inhibition include the inhibition of single strand break repair, PARP trapping, and the upregulation of non-homologous end joining. Olaparib and talazoparib are PARP inhibitors that have been approved for the management of HER2-negative breast cancer in patients with germline BRCA1/2 mutations. This review article highlights the clinical efficacy of PARP inhibitors in patients with HER2-negative breast cancer in early and advanced settings.

Diagnosis, Management, and Surveillance for Patients With PALB2, CHEK2, and ATM Gene Mutations.

BACKGROUND: This study aims to capture clinical and surgical practice patterns of patients with deleterious mutations in partner and localizer of BRCA2 (PALB2), checkpoint kinase 2 (CHEK2) and ataxia telangiesctasia mutated (ATM) genes. MATERIALS AND METHODS: This study is a retrospective chart review of patients with PALB2, CHEK2 or ATM mutations. Patient demographics, testing indications, management decisions, and surveillance strategies were recorded. RESULTS: Sixty-two patients were found to have deleterious mutations: 14 (23%) with a PALB2 mutation, 30 (48%) with a CHEK2 mutation, and 18 (29%) patients with an ATM mutation. Thirty-one (50%) patients have a history of breast cancer. Twenty-three patients were diagnosed and treated prior to genetic testing while 8 patients learned of their mutation status and breast cancer diagnosis simultaneously. Of these 8 patients, 4 sought treatment at our institution, 3 underwent bilateral mastectomy, and 1 patient opted for lumpectomy and surveillance. Thirty-one patients had no history of breast cancer. After genetic diagnosis, 3 of the 9 patients who continued clinical follow-up proceeded with bilateral prophylactic mastectomy within 2 years. Clinical surveillance continued for 23 months on average. CONCLUSION: Most patients who learned of their genetic and breast cancer diagnoses simultaneously underwent bilateral mastectomy, whereas only a third of patients without cancer opted for bilateral prophylactic mastectomy.

Reconstructive complications and early toxicity in breast cancer patients treated with proton-based postmastectomy radiation therapy.

Background: Postmastectomy radiation therapy (PMRT) decreases the risk of locoregional recurrence and increases overall survival rates in patients with high-risk node positive breast cancer. While the number of breast cancer patients treated with proton-based PMRT has increased in recent years, there is limited data on the use of proton therapy in the postmastectomy with reconstruction setting. In this study, we compared acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT. Methods: A retrospective review of our institutional database was performed to identify breast cancer patients treated with mastectomy with implant or autologous reconstruction followed by PMRT from 2015 to 2020. Baseline clinical, disease, and treatment related factors were compared between the photon-based and proton-based PMRT groups. Early toxicity outcomes and reconstructive complications following PMRT were graded by the treating physician. Results: A total of 11 patients treated with proton-based PMRT and 26 patients treated with photon-based PMRT were included with a median follow-up of 7.4 months (range, 0.7-33 months). Six patients (55%) in the proton group had a history of breast cancer (3 ipsilateral and 3 contralateral) and received previous RT 38 months ago (median, range 7-85). There was no significant difference in mean PMRT (p = 0.064) and boost dose (p = 0.608) between the two groups. Grade 2 skin toxicity was the most common acute toxicity in both groups (55% and 73% in the proton and photon group, respectively) (p = 0.077). Three patients (27%) in the proton group developed grade 3 skin toxicity. No Grade 4 acute toxicity was reported in either group. Reconstructive complications occurred in 4 patients (36%) in the proton group and 8 patients (31%) in photon group (p = 0.946). Conclusions: Acute skin toxicity remains the most frequent adverse event in both proton- and photon-based PMRT. In our study, reconstructive complications were not significantly higher in patients treated with proton- versus photon-based PMRT. Longer follow-up is warranted to assess late toxicities.

Uveitis, a rare but important complication of adjuvant zoledronic acid for early-stage breast cancer.

Bisphosphonates such as zoledronic acid are an important part of adjuvant therapy to reduce the risk of recurrence in early-stage breast cancer. Uveitis remains one of the lesser-known side effects of zoledronic acid; prompt recognition is essential to ensure patients receive appropriate and timely care to help prevent permanent vision loss. We report a case of anterior uveitis in a postmenopausal woman who presented with visual symptoms after receiving the first dose of zoledronic acid. This case report serves to educate and increase awareness of the risk of uveitis in patients who are given zoledronic acid. This is the first and only reported case of zoledronic acid when used in the adjuvant setting for the treatment of breast cancer.

Early Toxicity and Patient-Reported Cosmetic Outcomes in Patients Treated With Adjuvant Proton-Based Radiotherapy After Breast-Conserving Surgery.

INTRODUCTION: To evaluate the dosimetric data, early toxicity, and patient-reported cosmetic outcomes in breast cancer patients treated with adjuvant proton-based radiotherapy (RT) after breast-conserving surgery. MATERIALS AND METHODS: We performed a retrospective review of our institutional database to identify breast cancer patients treated with breast-conserving surgery followed by proton-based RT from 2015 to 2020. Patient-reported cosmetic outcomes were graded as excellent, good, fair, or poor. Early toxicity outcomes were graded by the treating physician during treatment. Dose-volume histograms were reviewed to obtain dosimetry data. RESULTS: We identified 21 patients treated with adjuvant proton-based RT. Median whole breast dose delivered was 46.8 Gy (range, 40.0-50.4 Gy). Target volumes included the regional lymph nodes in 17 patients (81%). Seventeen patients (81%) received a lumpectomy boost. The median planning target volume V95 was 94% (range, 77%-100%), V100 71% (range, 60%-97%), V110 2% (range 0%-18%), and median max point dose was 115% (range, 105%-120%). The median ipsilateral breast V105 was 367.3 cc (range, 0-1172 cc) and V110 was 24.1 cc (range, 0-321.3 cc). Grade 2 and 3 dermatitis occurred in 62% and 14% of patients, respectively. Grade 2 and 3 pain was reported by 33% and 10% of patients, respectively. Median follow-up at the time of cosmetic evaluation was 27 months (range, 5-42 months). Four patients (21%) reported fair cosmetic outcome and 15 patients (79%) reported good or excellent cosmetic outcome. No poor cosmesis was reported. CONCLUSION: Adjuvant proton-based radiotherapy after breast-conserving surgery is well tolerated with acceptable rates of acute toxicities and a high rate of good-to-excellent patient-reported cosmetic outcomes.

The Use of Intraoperative Ultrasound During Breast Conserving Surgery.

OBJECTIVES: The purpose of this study is to evaluate the utilization of intraoperative ultrasound (IOUS) for tumor localization in breast-conserving surgery and to examine its impact on margin positivity and re-excision rates. Additionally, the study seeks to identify factors contributing to surgeon utilization of IOUS. METHODS: A retrospective chart review was conducted of patients with preoperative diagnosis of breast cancer undergoing breast-conserving surgery by breast surgeons at multiple centers within a single healthcare system. Characteristics such as lesion size, palpability, histology, receptor status, and use of neoadjuvant chemotherapy were recorded. Re-excision rates were determined based on localization technique and surgeons' status of breast ultrasound certification. RESULTS: A total of 671 cases were performed, with 322 meeting study inclusion. 57 cases utilized IOUS, 250 utilized preoperative wire-guided localization (WGL), 10 used both methods and 5 cases used neither method. There was no significant difference in re-excision rates between IOUS and WGL or among the four surgeons. Ultrasound-certified surgeons were more likely to utilize IOUS, and re-excision rates trended higher for WGL, which may be clinically significant. CONCLUSION: Increasing familiarity with and utilization of IOUS during breast-conserving surgery may be clinically advantageous over traditional localization techniques. Ultrasound certification may lead to increased use of IOUS among surgeons.

Incidence of clinical lymphedema in breast cancer patients treated with adjuvant proton-based radiotherapy.

Background: The purpose of this study was to evaluate the incidence of clinical lymphedema following adjuvant proton-based radiotherapy (RT) in breast cancer (BC) patients. Materials and methods: We performed a retrospective review of our institutional database to identify BC patients treated with adjuvant proton-based RT. Patients receiving re-irradiation for a BC recurrence or those with a history of ipsilateral chest wall radiation were excluded. Clinical lymphedema was determined by documentation in the chart at baseline and during follow-up. Results: We identified 28 patients treated with adjuvant proton-based RT who met the study criteria. Median age at diagnosis was 45 (range, 24-75). Eleven patients (39%) underwent mastectomy, and fourteen (50%) underwent axillary lymph node dissection (ALND). Median number of LNs removed was 6 (range, 1-28). Nineteen patients (68%) received neoadjuvant chemotherapy. Median whole breast/chest wall dose delivered was 50 Gy (range, 44-54.0 Gy). Target volumes included the axillary and supraclavicular lymph nodes in all patients and internal mammary lymph nodes in 27 (96%) patients. Mean dose to the axilla was 49.7 Gy, and mean dose to 95% of the axillary volume (D95) was 46.3 Gy (94% of prescription dose). Mean dose to supraclavicular (SCV) volume was 47.7 Gy, and D95 was 44.1 Gy (91% of prescription dose). Grade 3 dermatitis occurred in 14% of patients. Five patients (18%) had clinical lymphedema, 4 from the ALND subset (n = 14). Conclusions: The incidence of clinical lymphedema after proton-based RT is comparable to rates reported with photon-based RT with comprehensive nodal coverage.

Patterns of postmastectomy radiation therapy in clinically node-positive breast cancerpatients with pathologically negative lymph nodes after neoadjuvant chemotherapy.

BACKGROUND: To analyze postmastectomy radiation therapy (PMRT) utilization and its association with overall survival (OS) in patients presenting with node-positive breast cancer who are pathologically node-negative (ypN0) after neoadjuvant chemotherapy (NAC). METHODS: Using the National Cancer Data Base (NCDB), we identified patients diagnosed between 2004 and 2013 with clinical T1-4 node-positive nonmetastatic breast cancer who received NAC and underwent mastectomy with pathologically negative lymph node sampling. Multivariable regression models identified factors associated with PMRT use. The Cox proportional hazards model was used to evaluate predictors of mortality. RESULTS: The study included 8766 clinically node-positive patients who met the study criteria. PMRT was delivered to 61.5% of patients. Overall PMRT utilization rate increased over the study period from 54.4% in 2004 to 65.2% in 2011. Predictors of PMRT use included larger tumor size, increasing clinical N stage, higher grade disease, receipt of hormone therapy, and a greater number of lymph nodes examined. The unadjusted 5-year OS was 84.1% in the PMRT group and 83.8% in the non-PMRT group (p = NS). PMRT was not significantly associated with survival on multivariable analysis (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.73-1.03). DISCUSSION: The delivery of PMRT has increased over time in women presenting with clinically node-positive breast cancer who convert to ypN0 after NAC. While we identified multiple independent socioeconomic and clinical predictors of both PMRT utilization and survival, PMRT itself was not significantly associated with survival.

Does the Use of BioZorb® Result in Smaller Breast Seroma Volume?

AIM: To evaluate the impact of BioZorb®, a 3D-bioabsorbable marker, on the tumor-bed boost volume and dosimetric parameters in adaptive boost planning for breast cancer. PATIENTS AND METHODS: Records were reviewed for 51 breast-cancer patients who underwent breast-conserving surgery and adjuvant whole-breast irradiation between January 2017 and October 2018. Changes in lumpectomy boost volume (LBV), doses to organs at risk, toxicity and cosmesis were compared between patients with and without BioZorb® Chi-square test and paired and independent t-tests were used for comparisons of variables. RESULTS: Median follow-up was 35.5 months. Mean LBV on initial CT (LBV1; 32.2 vs. 33.8 cc, p=0.74) and on boost computed tomography (CT) (LBV2; 25.3 vs. 24.8 cc, p=0.87) were similar with and without BioZorb® The mean decrease from LBV1 to LBV2 was 9.0 cc and 6.8 cc with and without BioZorb®, respectively (p=0.42). LBV1 was significantly positively correlated with a 20% reduction in LBV (p=0.02). Mean heart and lung doses on adaptive boost planning CT were slightly lower compared to initial planning CT in both groups. Acute breast pain was reported in 18/51 patients, 9 of whom had BioZorb® (p=0.24). Grade-2 pain was reported in 5/51 patients, 3 of whom had BioZorb® (p=0.11). Excellent or good cosmesis was reported in 36/41 patients. Fair cosmesis was reported in 5/41 patients, of whom 2 had BioZorb® (p=0.64). CONCLUSION: BioZorb® placement does not impact the tumor-bed boost volume nor the variation of seroma volume within the period of treatment. More data and longer follow-up are needed to identify a measurable clinical impact of BioZorb® placement.

Risk Factors for the Development of Clinical and Subclinical Lymphedema Detected by Bioimpedance Spectroscopy.

BACKGROUND: Breast cancer-related lymphedema can significantly compromise quality of life. Bioimpedance spectroscopy (BIS) measures extracellular fluid in lymphedema. The purpose of this study was to determine the incidence of BIS-detected lymphedema using the L-Dex and identify risk factors associated with a positive score. MATERIALS AND METHODS: We performed a retrospective review of our institutional database to identify patients who underwent L-Dex U400 measurements. Patients with a score of > 10 L-Dex units or with an increase of > 10 units from baseline had a positive score. Clinical lymphedema was determined by documentation in the chart at the time of positive measurement. Otherwise, patients were considered to have subclinical lymphedema. RESULTS: Fifty-three patients met study criteria. Thirty patients (56.6%) underwent mastectomy, 22 (41.5%) axillary lymph node dissection (ALND), and 33 (62.3%) received radiation (RT). Twelve patients (22.6%) had a positive score. There were no differences in age, race, laterality, breast surgery, T stage, N stage, chemotherapy, or RT fields (none, breast only, breast with LNs) in patients with a positive score. ALND was more common (66.7% vs. 34.2%, P= .04). BMI > 30 approached significance (58.3% vs. 29.3%, P= .06). Seven patients had subclinical lymphedema. No differences were identified comparing patients with subclinical lymphedema to those with negative scores. All 5 patients with clinical lymphedema underwent ALND and received nodal RT. CONCLUSION: The combination of ALND and regional nodal RT is strongly associated with development of clinical lymphedema. It is difficult to identify patients at risk for subclinical BIS-detected lymphedema.

Breast intraductal nanoformulations for treating ductal carcinoma in situ II: Dose de-escalation using a slow releasing/slow bioconverting prodrug strategy.

Ductal carcinoma in situ (DCIS) represents approximately 20-25% of newly diagnosed breast cancers. DCIS is treated by surgery and possibly radiotherapy. Chemotherapy is only used as adjuvant or neoadjuvant therapy but not as primary therapy. The present study investigated the intraductal administration of Ciclopirox (CPX) formulated in nanosuspensions (NSs) or nanoparticles (NPs) to treat DCIS locally in a Fischer 344 rat model orthotopically implanted with 13762 Mat B III cells. Slow converting esterase responsive CPX prodrugs (CPDs) were successfully synthesized at high purity (> 95%) by directly acetylating the hydroxyl group or by appending a self-immolative linker between CPX and a phenolic ester. Direct esterification CPDs were not sufficiently stable so self-immolative CPDs were formulated in NSs and NPs. Prodrug release was evaluated from poly(lactic-co-glycolic acid) NPs, and CPD4 demonstrated the slowest release rate with the rank order of CPD2 (R = methyl) > CPD3 (R = t-butyl) > CPD4 (R = phenyl). Intraductally administered CPX NS, CPD4 NS, and an innovative mixture of CDP4 NS and NPs (at 1 mg CPX equivalent/duct) demonstrated significant (p < 0.05) in vivo anti-tumor efficacy compared with immediate release (IR) CPX NS and non-treated controls. CPX mammary persistence at 6 h and 48 h after CPD4 NS or NP administration was also greater than after the immediate release CPX NS. A strong correlation between CPX mammary persistence and efficacy is demonstrated. In conclusion, nanoformulations utilizing a slow releasing/slow bioconverting CPX prodrug delivery strategy resulted in significant dose de-escalation (~ five fold) while maintaining anti-tumor efficacy.

Adaptive Lumpectomy Boost Planning Can Reduce Normal Tissue Exposure in Patients Receiving Hypofractionated Whole Breast Irradiation.

BACKGROUND/AIM: To evaluate the change in lumpectomy cavity (LPC) volume during hypofractionated radiation (Hypo-RT) and assess the dosimetric benefits of adaptive boost planning on normal tissue exposure in breast cancer patients. PATIENTS AND METHODS: Two separate computed tomography (CT) simulation scans were obtained. The first (CT1) was used to plan whole breast irradiation, and the second (CT2) was used to plan LPC boost. LPC boost treatment planning was performed on both CT1 and CT2. RESULTS: Mean LPC volume was significantly smaller on CT2 compared to CT1. LPC boost plan comparison showed significant reductions from CT1 to CT2 in mean heart dose and mean lung dose. Mean volume of tissue receiving 95% of the prescribed boost dose (V95) was lower on CT2 (p=0.001), as was V80 (p<0.001) and V50 (p<0.001). CONCLUSION: LPC volume can change significantly during Hypo-RT. Adaptive LPC boost planning can be considered to reduce normal tissue exposure.

Toxicities and Locoregional Control After External Beam Chest Wall and/or Regional Lymph Node Re-irradiation for Recurrent Breast Cancer.

BACKGROUND/AIM: To evaluate toxicities and clinical outcomes in breast cancer (BC) patients who underwent external beam chest wall (CW) and/or regional lymph node (LN) re-irradiation (re-RT) for locoregional recurrence (LRR). PATIENTS AND METHODS: We performed a retrospective review of our institutional database to identify BC patients diagnosed with an isolated ipsilateral CW or nodal recurrence after prior whole breast/CW irradiation. RESULTS: Fifteen patients met the study criteria. Median time between completion of RT courses was 68.3 months (range=7.8-245.4 months). Median CW re-RT dose was 45 Gy (range=42.3-50.4 Gy). The majority of patients (80%) received proton beam re-RT. Grade 2-3 dermatitis occurred in 87% patients. Grade 2-3 pain was reported by 33% of patients. At a median follow-up of 14 months (range=1.0-90.5 months), the rate of isolated LRR was 13%. CONCLUSION: Re-RT of the CW and/or regional LNs is feasible with acceptable rates of toxicity and low rates of isolated LRR.

Patterns of post-mastectomy radiation therapy in clinically node positive breast cancer patients with pathologically negative lymph nodes after neoadjuvant chemotherapy.

BACKGROUND: To analyze postmastectomy radiation therapy (PMRT) utilization and its association with overall survival (OS) in patients presenting with node positive breast cancer who are pathologically node negative (ypN0) after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Using the National Cancer Data Base (NCDB), we identified patients diagnosed between 2004 and 2013 with clinical T1-4 node-positive non-metastatic breast cancer who received NAC and underwent mastectomy with pathologically negative lymph node sampling. Multivariable regression models identified factors associated with PMRT use. The Cox proportional hazards model was used to evaluate predictors of mortality. RESULTS: The study included 8,766 clinically node-positive patients who met the study criteria. PMRT was delivered to 61.5% of patients. Overall PMRT utilization rate increased over the study period from 54.4% in 2004 to 65.2% in 2011. Predictors of PMRT use included larger tumor size, increasing clinical N stage, higher grade disease, receipt of hormone therapy, and greater number of lymph nodes examined. Unadjusted 5-year OS was 84.1% in the PMRT group and 83.8% in the non-PMRT group (p=NS). PMRT was not significantly associated with survival on multivariable analysis (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.73-1.03). CONCLUSION: The delivery of PMRT has increased over time in women presenting with clinically node positive breast cancer who convert to ypN0 after NAC. While we identified multiple independent socioeconomic and clinical predictors of both PMRT utilization and survival, PMRT itself was not significantly associated with survival.

Utilization of Hypofractionated Whole-Breast Radiotherapy With Concurrent Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Therapy.

INTRODUCTION: Hypofractionated radiotherapy (Hypo-RT) is now considered the standard of care for the majority of patients receiving whole-breast irradiation (WBI). However, there are few data on the use of Hypo-RT in human epidermal growth factor receptor 2 (HER2)-positive patients receiving concurrent anti-HER2 therapy. In this study, we sought to examine patterns of WBI in HER2-positive patients. PATIENTS AND METHODS: Using the National Cancer Data Base, we identified women with nonmetastatic HER2-positive breast cancer diagnosed between 2010 and 2015 who received WBI. The Hypo-RT group was defined as those receiving 21 or fewer fractions. All other patients were in the conventional radiotherapy (RT) group. Multivariate logistic regression was used to identify predictors of Hypo-RT utilization. Five-year overall survival was estimated by the Kaplan-Meier method. RESULTS: The study included 15,776 patients, of whom 17.7% received Hypo-RT. The rate of Hypo-RT utilization increased from 7.4% in 2010 to 29.3% in 2015 (P = .004). Predictors of Hypo-RT use included older age (≥60 vs. < 60 years), higher median income quartile, further distance from the treatment facility (>50 vs. ≤50 miles), treatment at an academic facility, and later year of diagnosis. Unadjusted 5-year overall survival rates were similar among patients who received Hypo-RT and conventional RT (93.9% vs. 95.2%, P = .26). After adjusting for patient, facility, and tumor variables, Hypo-RT was not significantly associated with survival. CONCLUSION: Although Hypo-RT was not commonly delivered in patients with HER2-positive breast cancer, the utilization rate quadrupled over the study period. Multiple socioeconomic and clinical predictors of Hypo-RT receipt were identified. Adjuvant RT regimen was not significantly associated with overall survival.

Breast intraductal nanoformulations for treating ductal carcinoma in situ I: Exploring metal-ion complexation to slow ciclopirox release, enhance mammary persistence and efficacy.

INTRODUCTION: Ductal Carcinoma In Situ (DCIS) represents a significant fraction (~20-25%) of all newly diagnosed breast cancer cases and, if left untreated, a significant fraction of patients will progress to invasive disease. Surgery is the only treatment option. Ciclopirox (CPX), an FDA-approved antifungal drug, has exhibited promising antitumor activity by down-regulating the expression of vital antiapoptotic cellular proteins and inhibiting the genetic expression of several oncogenic pathways. In this study, the feasibility of using nanoscale delivery systems to control release and prolong mammary tissue persistence of a lipophilic metal complex of CPX and Zinc (CPXZn) after intraductal administration was investigated. METHODS: CPX and CPX-Zn nanosuspensions (NSs) were prepared using an evaporative nanoprecipitation-ultra-sonication method. Flash nanoprecipitation was used to prepare PLGA nanoparticles (NPs) loaded with CPXZn. Our established orthotopic DCIS rat model was used to evaluate efficacy. Briefly, two days after 13762 Mat B III cell intraductal inoculation, rats were divided into treatment groups and a single intraductal injection of CPX NS, CPX-Zn NS or CPX-Zn NPs was administered. In the first study arm, the efficacy of CPX NS (1, 3, 5 mg/duct) was evaluated. In the second arm, the in vivo efficacy of CPX NS, CPX-Zn NS and CPX-Zn loaded NPs was evaluated and compared at equivalent CPX doses. The mammary persistence of CPX from CPX NS, CPX-Zn NS, and CPX-Zn PLGA NPs was also assessed. RESULTS: CPX-Zn complex was successfully synthesized and characterized by several spectral analyses. CPX release was slowed from the CPX-Zn NS and further slowed by incorporating CPX-Zn into PLGA NPs as compared to the CPX NS with release half times following the order: CPX NS < CPX-Zn NS << CPX-Zn NP. Intraductal CPX NS administration was dose and time dependent in suppressing tumor initiation suggesting prolonged mammary exposure may improve efficacy. In the second arm, mammary tissue persistence of CPX followed the rank order CPX NS < CPX-Zn NS << CPX-Zn NP at 6 h and 48 h post-administration. Prolonged mammary CPX exposure was highly correlated to improved efficacy. Prolonged CPX tissue persistence, attributed to slower release from the zinc complex and the PLGA NPs, resulted in a 5-fold dose reduction compared to the CPX NS. CONCLUSIONS: The current results demonstrate that slowing drug release in the mammary duct after intraductal administration overcomes the rapid ductal clearance of CPX, prolongs mammary tissue persistence, improves efficacy against DCIS lesions in vivo, and requires 5-fold less CPX to achieve equivalent efficacy. The studies also provide a strategic path forward for developing a locally administered drug delivery system for treating DCIS, for which no primary chemotherapy option is available.

Metaplastic Carcinoma of the Breast Is More Aggressive Than Triple-negative Breast Cancer: A Study From a Single Institution and Review of Literature.

BACKGROUND: We aimed to describe our experience with metaplastic breast carcinoma (MBC), evaluate its clinical outcome compared with triple-negative breast cancer (TNBC), and provide a through and comprehensive review of the literature to date. MATERIALS AND METHODS: We reviewed MBC cases (n = 46) from our institution. The following variables were recorded: tumor histologic subtype, Nottingham grade, tumor size, lymph node status, Tumor, Node, Metastases stage, biomarkers profile, patient's age and race, therapy modality (chemotherapy and radiation), and survival (disease-free survival [DFS] and overall survival [OS]). The clinical and pathological data for TNBC (n = 508) cases were extracted from the breast cancer database. To compare the survival between MBC and TNBC, a subgroup of MBC cases (n = 40) were matched with TNBC cases (n = 40) on the basis of known prognostic confounders. RESULTS: There were 17 of 46 (37%) cases with mesenchymal differentiation, 12 (26.1%) squamous cell carcinoma, 14 (30.4%) spindle cell carcinoma, and 3 (6.5%) mixed type. MBC presented at a more advanced stage than TNBC (P = .014) and was more likely to recur (34% vs. 15.5%; P = .004). More MBC patients died from disease than TNBC (29% vs. 16%; P = .05). In the multivariate analysis, MBC had approximately twice the risk of local recurrence than TNBC (95% confidence interval, 1.01-3.83; P = .05). MBC patients had worse DFS and OS than the matched TNBC patients (P < .001 and P = .033, respectively). A review of the literature comparing MBC versus TNBC is presented. CONCLUSION: Our results suggest that MBC is clinically more aggressive than TNBC. Further studies might help delineate the differences between these 2 entities.

Impact of American College of Surgeons Oncology Group Z11 on surgical training at an academic cancer center.

BACKGROUND: The application of the American College of Surgeons Oncology Group Z0011 trial (Z11) has resulted in fewer completion axillary lymph node dissections (ALNDs) for select patients. We hypothesize that the application of Z11 may result in fewer ALND cases for surgeons in training. METHODS: In the setting of an academic cancer center incorporating Z11 into routine practice, we compared the total number of ALND performed in a pre-Z11 period (January 2007-April 2011, 52 mo) and post-Z11 period (April 2011-February 2014, 34 mo). We also identified the number of patients in the post-Z11 era in whom ALND was omitted as a result of Z11. Clinical and pathologic characteristics among these groups were analyzed. RESULTS: A total of 279 and 191 ALNDs were performed in the pre-Z11 and post-Z11 groups, respectively. Variables were similar among these groups with respect to demographics, tumor characteristics, and surgeries performed. There was no difference in the monthly rates of ALND between groups-5.37 cases/mo (pre-Z11) and 5.62 cases/mo (post-Z11), P = 0.52. We identified a total of 53 patients for whom ALND was omitted due to Z11 application in the post-Z11 period, representing a potential 21.7% decrease (53/191 + 53) in the number of ALNDs in this period. CONCLUSIONS: Although the application of Z11 could potentially impact surgical training with a 21.7% decrease in ALND cases (53/191 + 53), the surgical case volume at an academic cancer center absorbs this decrease and maintains consistent levels of training for ALND.