One-Year Experience of Same-Day Mastectomy and Breast Reconstruction Protocol.

BACKGROUND: The prevalence of same-day mastectomy with reconstruction has continued to increase across the United States in recent years. Prior studies have shown that same-day mastectomy with reconstruction leads to increased patient satisfaction and allows hospitals to use resources better. This study sought to evaluate the implementation of same-day mastectomy with a reconstruction recovery protocol for patients undergoing mastectomy at our institution. METHODS: Under an institutional review board-approved protocol, a retrospective cohort analysis compared patients who underwent mastectomy April 2016 through April 2017 with those who had mastectomy March 2020 through March 2021. Length of stay, postoperative intravenous (IV) opioid administration, safety end points, and cost were the main variables examined. RESULTS: The study compared 457 patients in 2016-2017 with 428 patients in 2020-2021. The median hospital length of stay decreased from 24.6 h in 2016-2017 to 5.5 h in 2020-2021 (p < 0.001). The percentage of patients requiring postoperative IV opioids decreased from 69.1 % in 2016-2017 to 50 % in 2020-2021 (p < 0.001). The rates of unplanned readmissions within 30 days after mastectomy did not differ between the two groups, with a rate of 3.7 % in 2016-2017 and a rate of 5.1 % in 2020-2021 (p = 0.30). Reducing the rate of overnight admissions after mastectomy by 65.8 % resulted in a cost reduction of 65.8 %. CONCLUSIONS: Implementation of same-day mastectomy with a reconstruction protocol across a large academic center and two satellite sites was a safe alternative to conventional mastectomy recovery plans.

Phase II Study of Proton Beam Radiation Therapy for Patients With Breast Cancer Requiring Regional Nodal Irradiation.

PURPOSE: To evaluate the safety and efficacy of proton beam radiation therapy (RT) for patients with breast cancer who require regional nodal irradiation. METHODS: Patients with nonmetastatic breast cancer who required postoperative RT to the breast/chest wall and regional lymphatics and who were considered suboptimal candidates for conventional RT were eligible. The primary end point was the incidence of grade 3 or higher radiation pneumonitis (RP) or any grade 4 toxicity within 3 months of RT. Secondary end points were 5-year locoregional failure, overall survival, and acute and late toxicities per Common Terminology Criteria for Adverse Events (version 4.0). Strain echocardiography and cardiac biomarkers were obtained before and after RT to assess early cardiac changes. RESULTS: Seventy patients completed RT between 2011 and 2016. Median follow-up was 55 months (range, 17 to 82 months). Of 69 evaluable patients, median age was 45 years (range, 24 to 70 years). Sixty-three patients (91%) had left-sided breast cancer, two had bilateral breast cancer, and five had right-sided breast cancer. Sixty-five (94%) had stage II to III breast cancer. Sixty-eight (99%) received systemic chemotherapy. Fifty (72%) underwent immediate reconstruction. Median dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the internal mammary nodes, 48.8 Gy (relative biological effectiveness), which indicates comprehensive coverage. Among 62 surviving patients, the 5-year rates for locoregional failure and overall survival were 1.5% and 91%, respectively. One patient developed grade 2 RP, and none developed grade 3 RP. No grade 4 toxicities occurred. The unplanned surgical re-intervention rate at 5 years was 33%. No significant changes in echocardiography or cardiac biomarkers after RT were found. CONCLUSION: Proton beam RT for breast cancer has low toxicity rates and similar rates of disease control compared with historical data of conventional RT. No early cardiac changes were observed, which paves the way for randomized studies to compare proton beam RT with standard RT.

Implications of New Lumpectomy Margin Guidelines for Breast-Conserving Surgery: Changes in Reexcision Rates and Predicted Rates of Residual Tumor.

BACKGROUND: The 2014 guidelines endorsed by Society of Surgical Oncology, the American Society of Breast Surgeons, and the American Society for Radiation Oncology advocate "no ink on tumor" as the new margin requirement for breast-conserving therapy (BCT). We used our lumpectomy margins database from 2004 to 2006 to predict the effect of these new guidelines on BCT. METHODS: Patients with neoadjuvant therapy, pure ductal carcinoma-in situ, or incomplete margin data were excluded. We applied new ("no ink on tumor") and old (≥2 mm) margin guidelines and compared rates of positive margins, reexcision, and rates of residual disease found at reexcision. RESULTS: A total of 437 lumpectomy surgeries met the eligibility criteria. Eighty-six percent had invasive ductal carcinoma, 12% invasive lobular carcinoma, and 2% invasive ductal carcinoma and invasive lobular carcinoma. Using a ≥2 mm margin standard, 36% of lumpectomies had positive margins compared to 18% using new guidelines (p < 0.0001). Seventy-seven percent of patients with "ink on tumor" had residual disease found at reexcision. Fifty percent of subjects with margins <2 mm had residual disease (p = 0.0013) but would not have undergone reexcision under the new guidelines. With margins of ≥2 mm, residual tumor was seen in the shaved margins of 14% of lumpectomies. Residual tumor was more common in reexcisions for ductal carcinoma-in situ <2 mm from a margin than for invasive cancer (53 vs. 40%), although this was not statistically significant. CONCLUSIONS: Use of new lumpectomy margin guidelines would have reduced reoperation for BCT by half in our patient cohort. However, residual disease was present in many patients who would not have been reexcised with the new guidelines. Long-term follow-up of local recurrence rates is needed to determine if this increase in residual disease is clinically significant.

External beam accelerated partial-breast irradiation using 32 gy in 8 twice-daily fractions: 5-year results of a prospective study.

PURPOSE: External beam accelerated partial breast irradiation (APBI) is an increasingly popular technique for treatment of patients with early stage breast cancer following breast-conserving surgery. Here we present 5-year results of a prospective trial. METHODS AND MATERIALS: From October 2003 through November 2005, 98 evaluable patients with stage I breast cancer were enrolled in the first dose step (32 Gy delivered in 8 twice-daily fractions) of a prospective, multi-institutional, dose escalation clinical trial of 3-dimensional conformal external beam APBI (3D-APBI). Median age was 61 years; median tumor size was 0.8 cm; 89% of tumors were estrogen receptor positive; 10% had a triple-negative phenotype; and 1% had a HER-2-positive subtype. Median follow-up was 71 months (range, 2-88 months; interquartile range, 64-75 months). RESULTS: Five patients developed ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial IBTR rate of 5% (95% confidence interval [CI], 1%-10%). Three of these cases occurred in patients with triple-negative disease and 2 in non-triple-negative patients, for 5-year actuarial IBTR rates of 33% (95% CI, 0%-57%) and 2% (95% CI, 0%-6%; P<.0001), respectively. On multivariable analysis, triple-negative phenotype was the only predictor of IBTR, with borderline statistical significance after adjusting for tumor grade (P=.0537). CONCLUSIONS: Overall outcomes were excellent, particularly for patients with estrogen receptor-positive disease. Patients in this study with triple-negative breast cancer had a significantly higher IBTR rate than patients with other receptor phenotypes when treated with 3D-APBI. Larger, prospective 3D-APBI clinical trials should continue to evaluate the effect of hormone receptor phenotype on IBTR rates.

Support needs and acceptability of psychological and peer consultation: attitudes of 108 women who had undergone or were considering prophylactic mastectomy.

OBJECTIVE: Prophylactic mastectomy (PM) offers 90% or greater reduction in risk of breast cancer to women at increased hereditary risk. Nonetheless, acceptance in North America is low (0-27%) and 25-50% of women electing surgery report psychological distress and/or difficulty adapting following PM. Most women also report reduced cancer worry postoperatively. Psychological consultation to aid decision-making and post-surgical coping is not routinely offered. This retrospective, cross-sectional study explored interest in and acceptability of psychological consultation for issues related to PM among 108 women who had undergone or were considering surgery. METHOD: Qualitative interviews were conducted with 26 healthy women who had undergone prophylactic mastectomy of both (bilateral) breasts (BPM), 45 women who had undergone prophylactic mastectomy of one breast (unilateral contralateral) (UPM) after diagnosis of invasive breast cancer in the other breast or ductal carcinoma in situ (DCIS), and 37 women who were considering having PM surgery. RESULTS: Of the women who had undergone PM, more than half felt pre-surgical psychological consultation was advisable; nearly 2/3 thought post-surgical psychological consultation would be helpful. All women currently considering PM believed psychological consultation would aid decision-making and preparation for surgery. Strong support was reported in all groups for the emotional and informational value of speaking with a woman who had previously undergone PM. CONCLUSIONS: Narratives illustrate the nature and intensity of the need for psychological support and describe preferences for the role of the psychologist. Suggestions are offered for integration of psychological services for women deciding about or adapting to PM.

The role of the cyclin D1-dependent kinases in ErbB2-mediated breast cancer.

Intact cyclin D1 functions are essential for transformation by erbB2 in tissue culture and murine models. Because cyclin D1 may alter cell proliferation through a variety of mechanisms, we used transgenic models and human tumor samples to particularly address the role of cyclin D1-cyclin-dependent kinases in transformation by erbB2. The p16 tumor suppressor specifically blocks cyclin-dependent kinase 4 and 6 activity. Here we show that an MMTV-p16 transgene blocked tumorigenesis by erbB2, demonstrating that deregulation of the cyclin-dependent kinase partner of cyclin D1 is an essential target of erbB2. ErbB2 overexpression was a determining factor in deregulation of cyclin D1-cdk4/6 interactions because neither transgenic cyclin D1 nor loss of p16 accelerated tumorigenesis in MMTV-erbB2-transgenic mice. ErbB2 was also a deciding factor in deregulation of cyclin D1-cdk4/6 in human tumors because no loss of pRb or p16 was found in tumors overexpressing erbB2, although erbB2-negative invasive breast adenocarcinomas frequently lacked expression of p16 or pRb. We conclude that deregulation of cyclin D1-Cdk4/6 interactions is a critical target of erbB2 function in human and mouse breast tumors, and erbB2's overexpression may be sufficient to deregulate cyclin D1-cdk4/6 activity in breast cancer.

Lymphoscintigraphy and sentinel node biopsy accurately stage melanoma in patients presenting after wide local excision.

BACKGROUND: Patients have traditionally been considered candidates for sentinel node biopsy (SNBx) only at the time of wide local excision (WLE). We hypothesized that patients with prior WLE may also be staged accurately with SNBx. METHODS: Seventy-six patients, including 18 patients from the University of Virginia and 58 from a multicenter study of SNBx led by investigators at the University of Vermont, who had previous WLE for clinically localized melanoma underwent lymphoscintigraphy with SNBx. Median follow-up time was 38 months. RESULTS: Intraoperative identification of at least 1 sentinel node was accomplished in 75 patients (98.6%). The mean number of sentinel nodes removed per patient was 2.0. Eleven patients (15%) had positive sentinel nodes. Among the 64 patients with negative SNBx, 3 (4%) developed nodal recurrences in a sentinel node-negative basin simultaneous with systemic metastasis, and 1 (1%) developed an isolated first recurrence in a lymph node. CONCLUSIONS: This multicenter study more than doubles the published experience with SNBx after WLE and provides much-needed outcome data on recurrence after SNBx in these patients. These outcomes compare favorably with the reported literature for patients with SNBx at the time of WLE, suggesting that accurate staging of the regional lymph node bed is possible in patients after WLE.

Gene expression profiles of human breast cancer progression.

Although distinct pathological stages of breast cancer have been described, the molecular differences among these stages are largely unknown. Here, through the combined use of laser capture microdissection and DNA microarrays, we have generated in situ gene expression profiles of the premalignant, preinvasive, and invasive stages of human breast cancer. Our data reveal extensive similarities at the transcriptome level among the distinct stages of progression and suggest that gene expression alterations conferring the potential for invasive growth are already present in the preinvasive stages. In contrast to tumor stage, different tumor grades are associated with distinct gene expression signatures. Furthermore, a subset of genes associated with high tumor grade is quantitatively correlated with the transition from preinvasive to invasive growth.