Cheryl Ewing

Total Skin-sparing Mastectomy: Complications and Local Recurrence Rates in 2 Cohorts of Patients

Purpose:Dissemination of the total skin-sparing mastectomy (TSSM) technique is limited by concerns of nipple viability, flap necrosis, local recurrence risk, and the technical challenge of this procedure. We sought to define the impact of surgical and reconstructive variables on complication rates and assess how changes in technique affect outcomes. Patients and Methods:We compared the outcomes of TSSM in 2 cohorts of patients. Cohort 1: the first 64 TSSM procedures performed at our institution, between 2001 and 2005. Cohort 2: 106 TSSM performed between 2005 and 2007. Outcomes of cohort 1 were analyzed in 2005. At that time, potential risk factors for complications were identified, and efforts to minimize these risks by altering operative and reconstructive technique were then applied to patients in cohort 2. The impact of these changes on outcomes was assessed. Logistic regression was used to determine the association between predictor variables and adverse outcomes (Stata 10). Results:The predominant incision type in cohort 2 involved less than a third of the nipple areola complex (NAC), and the most frequent reconstruction technique was tissue expander placement. Between cohort 1 and cohort 2, nipple survival rates rose from 80% to 95% (P = 0.003) and complication rates declined: necrotic complications (30% → 13%; P = 0.01), implant loss (31% → 10%; P = 0.005), skin flap necrosis (16%–11%; not significant), and significant infections (17%–9%, not significant). Incisions involving >30% of the NAC (P < 0.001) and reconstruction with autologous tissue (P < 0.001) were independent risk factors for necrotic complications. The local recurrence rate was 0.6% at a median follow-up of 13 months (range, 1–65), with no recurrences in the NAC. Conclusion:Focused improvement in technique has resulted in the development of TSSM as a successful intervention at our institution that is oncologically safe with high nipple viability and early low rates of recurrence. Identifying factors that contribute to complications and changing surgical and reconstructive techniques to eliminate risk factors has greatly improved outcomes.

Adaptive Randomization of Veliparib–Carboplatin Treatment in Breast Cancer

BACKGROUND The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. METHODS In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. RESULTS With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. CONCLUSIONS The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

The effects of acellular dermal matrix in expander-implant breast reconstruction after total skin-sparing mastectomy: results of a prospective practice improvement study.

Background: Neither outcome after total skin-sparing mastectomy and expander-implant reconstruction using acellular dermal matrix nor a strategy for optimal acellular dermal matrix selection criteria has been well described. Methods: Prospective review of three patient cohorts undergoing total skin-sparing mastectomy with preservation of the nipple-areola complex and immediate expander-implant reconstruction from 2006 to 2010 was performed. Cohort 1 (no acellular dermal matrix) comprised 90 cases in which acellular dermal matrix was not used. Cohort 2 (consecutive acellular dermal matrix) included the next 100 consecutive cases, which all received acellular dermal matrix. Cohort 3 (selective acellular dermal matrix) consisted of the next 260 cases, in which acellular dermal matrix was selectively used based on mastectomy skin flap thickness. Complication rates were compared using chi-square analysis. Results: The study included 450 cases in 288 patients. Mean follow-up was 25.5 months. Infection occurred in 27.8 percent of the no–acellular dermal matrix cases, 20 percent of the consecutive cases, and 15.8 percent of the selective cases (p = 0.04). Unplanned return to the operating room was required in 23.3, 11, and 10 percent of cases, respectively (p = 0.004). Expander-implant loss occurred in 17.8, 7, and 5 percent of cases, respectively (p = 0.001). Additional analysis of the odds ratios of developing complications after postmastectomy radiation therapy demonstrated a specific protective benefit of acellular dermal matrix in irradiated patients. Conclusions: Acellular dermal matrix use in expander-implant reconstruction after total skin-sparing mastectomy reduced major postoperative complications in this study. Maximal benefit is achieved with selected use in patients with thin mastectomy skin flaps and those receiving radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Ethnicity and spirituality in breast cancer survivors.

IntroductionMany women are incorporating spirituality as a way of coping with cancer. However, few studies have examined the role of spirituality in mood and quality of life among breast cancer survivors from different ethnic groups.MethodsOne hundred and seventy-five women who had completed treatment for breast cancer participated in in-depth interviews about their experiences. Transcripts were available for 161 women.ResultsThe majority (83%) of the women talked about their spirituality. The main themes were: (1) God as a Comforting Presence; (2) Questioning Faith; (3) Anger at God; (4) Spiritual Transformation of Self and Attitude Towards Others/Recognition of Own Mortality; (5) Deepening of Faith; (6) Acceptance; and (7) Prayer by Self. A higher percentage of African-Americans, Latinas, and Christians felt comforted by God than the other groups.ConclusionsThese results are consistent with the common assumption that more African-American and Latinas engage in spiritual activities and that African-Americans are more fatalistic than the other groups. Implications for Cancer Survivors: The present findings suggest that there are several dimensions of spirituality experienced among cancer survivors. For many the trauma of a cancer diagnosis might deepen their faith and appreciation of life as well as changing the way they view at themselves, their lives, and how they relate to those around them, including God.

Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients

Accurate intraoperative pathologic examination of sentinel lymph nodes (SLNs) has been an important tool that can reduce the need for reoperations in patients with SLN‐positive breast cancer. The objective of the current study was to determine the accuracy of intraoperative frozen section (IFS) of SLNs during breast cancer surgery.

The Effect of Sentinel Node Tumor Burden on Non–Sentinel Node Status and Recurrence Rates in Breast Cancer

BackgroundRoutine axillary lymph node dissection (ALND) after selective sentinel lymphadenectomy (SSL) in the treatment of breast cancer remains controversial. We sought to determine the need for routine ALND by exploring the relationship between sentinel lymph node (SLN) and non-SLN (NSLN) status. We also report our experience with disease relapse in the era of SSL and attempt to correlate this with SLN tumor burden.MethodsThis was a retrospective study of 390 patients with invasive breast cancer treated at a single institution who underwent successful SSL from November 1997 to November 2002.ResultsOf the 390 patients, 115 received both SSL and ALND. The percentage of additional positive NSLNs in the SLN-positive group (34.2%) was significantly higher than in the SLN-negative group (5.1%; P = .0004). The SLN macrometastasis group had a significantly higher rate of positive NSLNs (39.7%) compared with the SLN-negative group (5.1%; P = .0001). Sixteen patients developed recurrences during follow-up, including 6.1% of SLN-positive and 3.3% of SLN-negative patients. Among the SLN macrometastasis group, 8.7% had recurrence, compared with 2.2% of SLN micrometastases over a median follow-up period of 31.1 months. One regional failure developed out of 38 SLN-positive patients who did not undergo ALND.ConclusionsALND is recommended for patients with SLN macrometastasis because of a significantly higher incidence of positive NSLNs. Higher recurrence rates are also seen in these patients. However, the role of routine ALND in patients with a low SLN tumor burden remains to be further determined by prospective randomized trials.

The benefits of prayer on mood and well-being of breast cancer survivors

ObjectivesPrayer is becoming more widely acknowledged as a way to cope with cancer. The goal of this study was to compare differences in use of prayer between breast cancer survivors from different ethnic groups and examine how use of prayer is related to mood and quality of life.MethodsThis study used a mixed methods design. One hundred and seventy-five breast cancer survivors participated in a longitudinal study of survivorship. Women completed in-depth qualitative interviews and a battery of measures including quality of life, spirituality, social support, and mood.ResultsEighty-one percent of the women prayed. There were no significant differences between the groups for any of the psychological, social support, or quality of life variables with the exception of higher benefit finding and spiritual well-being among those who prayed. The data did show that women who prayed were able to find more positive contributions from their cancer experience than women who did not pray. The interviews showed that those who prayed tended to be African American or Asian, Catholic or Protestant. The prayers were for petitioning, comfort, or praise. Some of the women stated that they had difficulty praying for themselves.ConclusionsWhile there seems to be few differences in terms of standardized measures of quality of life, social support, and mood between those who prayed and those who did not, the interviews showed that certain ethnic minority groups seem to find more comfort in prayer, felt closer to God, and felt more compassion and forgiveness than Caucasian women.

Older women, breast cancer, and social support

IntroductionOne in ten women over the age of 65 will develop breast cancer. Despite this high incidence of breast cancer among older women, social support for them is often inadequate. This paper describes a qualitative study of the impact of a breast cancer diagnosis on older women from racially/ethnically diverse populations and their subsequent need for social support.MethodsForty-seven older African American, Asian American, Caucasian and Latina women between the ages of 65 to 83 participated in a larger study examining the impact of breast cancer on women from racially/ethnically diverse populations and the meaning and nature of social support. The women completed an in-depth qualitative interview on the psychosocial impact of breast cancer and the meaning and nature of social support.Results and ConclusionThe results indicate that there are variations in reactions to a breast cancer diagnosis among older women, and that these reactions impact their experiences with seeking social support at diagnosis and during treatment. Respondents were concerned about their aging bodies, potential dependency on others, and loss of autonomy. At the same time, the severity of cancer treatment and existing co-morbidities often meant they needed to learn to receive support, and to reach out if they had no support. The implications of these findings underscore the older cancer patient’s need to strengthen her supportive networks at the time of diagnosis, during treatment, and post-treatment.

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.

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.