Susan L. Troyan

Skin-sparing mastectomy and immediate reconstruction : Oncologic risks and aesthetic results in patients with early-stage breast cancer

&NA; Skin‐sparing mastectomy has been advocated as an oncologically safe approach for the management of patients with early‐stage breast cancer that minimizes deformity and improves cosmesis through preservation of the skin envelope of the breast. Because chest wall skin is the most frequent site of local failure after mastectomy, concerns have been raised that inadequate skin excision could result in an increased risk of local recurrence. Precise borders of the skin resection have not been well established, and long‐term local recurrence rates after skin‐sparing mastectomy are not known. The purpose of this study was to evaluate the oncologic safety and aesthetic results for skin‐sparing mastectomy and immediate breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast prosthesis. Fifty‐one patients with early‐stage breast cancer (26 with ductal carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy and immediate reconstruction with a latissimus flap were studied from 1991 through 1994. For 32 consecutive patients, skin‐sparing mastectomy was defined as a 5‐mm margin of skin designed around the border of the nipple‐areolar complex. After the mastectomy, biopsies were obtained from the remaining native skin flap edges. Patients were followed for 44.8 months. Histologic examination of 114 native skin flap biopsy specimens failed to demonstrate breast ducts in the dermis of any of the 32 consecutive patients studied. One of 26 patients with ductal carcinoma in situ had metastases to the skin of the lateral chest wall and back. Four other patients, one with stage I disease and three with stage II‐B disease, had recurrent breast carcinoma. The stage I patient had a local recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients suffered axillary relapse, and one had distant metastases to the spine. The findings of this study support the technique of skin‐sparing mastectomy as an oncologically safe one, based on an absence of breast ductal epithelium at the margins of the native skin flaps and a local recurrence rate of 2 percent after 45 months of follow‐up. Although these results need to be confirmed with greater numbers of patients and longer follow‐up, skin‐sparing mastectomy and immediate breast reconstruction may be considered an excellent alternative treatment to breast conservation for patients with ductal carcinoma in situ and early‐stage invasive breast cancer. (Plast. Reconstr. Surg. 102: 49, 1998.)

Prospective Study of Wide Excision Alone for Ductal Carcinoma in Situ of the Breast

PURPOSE It has been hypothesized that wide excision alone with margins > or = 1 cm may be adequate treatment for small, grade 1 or 2 ductal carcinoma in situ (DCIS). To test this hypothesis, we conducted a prospective, single-arm trial. METHODS Entry criteria included DCIS of predominant grade 1 or 2 with a mammographic extent of < or = 2.5 cm treated with wide excision with final margins of > or = 1 cm or a re-excision without residual DCIS. Tamoxifen was not permitted. The accrual goal was 200 patients. RESULTS In July 2002, the study closed to accrual at 158 patients because the number of local recurrences met the predetermined stopping rules. The median age was 51 and the median follow-up time was 40 months. Thirteen patients developed local recurrence as the first site of treatment failure 7 to 63 months after study entry. The rate of ipsilateral local recurrence as first site of treatment failure was 2.4% per patient-year, corresponding to a 5-year rate of 12%. Nine patients (69%) experienced recurrence of DCIS and four (31%) experienced recurrence with invasive disease. Twelve recurrences were detected mammographically and one was palpable. Ten were in the same quadrant as the initial DCIS and three were elsewhere within the ipsilateral breast. No patient had positive axillary nodes at recurrence or subsequent metastatic disease. CONCLUSION Despite margins of > or = 1 cm, the local recurrence rate is substantial when patients with small, grade 1 or 2 DCIS are treated with wide excision alone. This risk should be considered in assessing the possible use of radiation therapy with or without tamoxifen in these patients.

Perceptions, Knowledge, and Satisfaction With Contralateral Prophylactic Mastectomy Among Young Women With Breast Cancer: A Cross-sectional Survey

UNLABELLED Chinese translation BACKGROUND Rates of contralateral prophylactic mastectomy (CPM) have increased dramatically, particularly among younger women with breast cancer, but little is known about how women approach the decision to have CPM. OBJECTIVE To examine preferences, knowledge, decision making, and experiences of young women with breast cancer who choose CPM. DESIGN Cross-sectional survey. SETTING 8 academic and community medical centers that enrolled 550 women diagnosed with breast cancer at age 40 years or younger between November 2006 and November 2010. PATIENTS 123 women without known bilateral breast cancer who reported having bilateral mastectomy. MEASUREMENTS A 1-time, 23-item survey that included items related to decision making, knowledge, risk perception, and breast cancer worry. RESULTS Most women indicated that desires to decrease their risk for contralateral breast cancer (98%) and improve survival (94%) were extremely or very important factors in their decision to have CPM. However, only 18% indicated that women with breast cancer who undergo CPM live longer than those who do not. BRCA1 or BRCA2 mutation carriers more accurately perceived their risk for contralateral breast cancer, whereas women without a known mutation substantially overestimated this risk. LIMITATIONS The survey, which was administered a median of 2 years after surgery, was not validated, and some questions might have been misinterpreted by respondents or subject to recall bias. Generalizability of the findings might be limited. CONCLUSION Despite knowing that CPM does not clearly improve survival, women who have the procedure do so, in part, to extend their lives. Many women overestimate their actual risk for cancer in the unaffected breast. Interventions aimed at improving risk communication in an effort to promote evidence-based decision making are warranted. PRIMARY FUNDING SOURCE Susan G. Komen for the Cure.

Treatment outcome after tangential radiation therapy without axillary dissection in patients with early-stage breast cancer and clinically negative axillary nodes

PURPOSE To determine the risk of nodal failure in patients with early-stage invasive breast cancer with clinically negative axillary lymph nodes treated with two-field tangential breast irradiation alone, without axillary lymph node dissection or use of a third nodal field. METHODS AND MATERIALS Between 1988 and 1993, 986 evaluable women with clinical Stage I or II invasive breast cancer were treated with breast-conserving surgery and radiation therapy. Of these, 92 patients with clinically negative nodes received tangential breast irradiation (median dose, 45 Gy) followed by a boost, without axillary dissection. The median age was 69 years (range, 49-87). Eighty-three percent had T1 tumors. Fifty-three patients received tamoxifen, 1 received chemotherapy, and 2 patients received both. Median follow-up time for the 79 survivors was 50 months (range, 15-96). Three patients (3%) have been lost to follow-up after 20-32 months. RESULTS No isolated regional nodal failures were identified. Two patients developed recurrence in the breast only (one of whom had a single positive axillary node found pathologically after mastectomy). One patient developed simultaneous local and distant failures, and six patients developed distant failures only. One patient developed a contralateral ductal carcinoma in situ, and two patients developed other cancers. CONCLUSION Among a group of 92 patients with early-stage breast cancer (typically T1 and also typically elderly) treated with tangential breast irradiation alone without axillary dissection, with or without systemic therapy, there were no isolated axillary or supraclavicular regional failures. These results suggest that it is feasible to treat selected clinically node-negative patients with tangential fields alone. Prospective studies of this approach are warranted.

Altered Proliferation and Differentiation Properties of Primary Mammary Epithelial Cells from BRCA1 Mutation Carriers

Female BRCA1 mutation carriers have a nearly 80% probability of developing breast cancer during their life-time. We hypothesized that the breast epithelium at risk in BRCA1 mutation carriers harbors mammary epithelial cells (MEC) with altered proliferation and differentiation properties. Using a three-dimensional culture technique to grow MECs ex vivo, we found that the ability to form colonies, an indication of clonality, was restricted to the aldehyde dehydrogenase 1-positive fraction in MECs but not in HCC1937 BRCA1-mutant cancer cells. Primary MECs from BRCA1 mutation carriers (n = 9) had a 28% greater ability for clonal growth compared with normal controls (n = 6; P = 0.006), and their colonies were significantly larger. Colonies in controls and BRCA1 mutation carriers stained positive for BRCA1 by immunohistochemistry, and 79% of the examined single colonies from BRCA1 carriers retained heterozygosity for BRCA1 (ROH). Colonies from BRCA1 mutation carriers frequently showed high epidermal growth factor receptor (EGFR) expression (71% EGFR positive versus 44% in controls) and were negative for estrogen receptor (ERalpha; 32% ER negative, 44% mixed, 24% ER positive versus 90% ER positive in controls). Expression of CK14 and p63 were not significantly different. Microarray studies revealed that colonies from BRCA1-mutant PMECs anticipate expression profiles found in BRCA1-related tumors, and that the EGFR pathway is up-regulated. We conclude that BRCA1 haploinsufficiency leads to an increased ability for clonal growth and proliferation in the PMECs of BRCA1 mutation carriers, possibly as a result of EGFR pathway activation. These altered growth and differentiation properties may render BRCA1-mutant PMECs vulnerable to transformation and predispose to the development of ER-negative, EGFR-positive breast cancers.

Development and implementation of a science training course for breast cancer activists: Project LEAD (leadership, education and advocacy development)

Objective To develop and implement Project LEAD (leadership, education, and advocacy development), a science course for breast cancer activists.

P4-11-10: Perceptions, Knowledge and Satisfaction with Contralateral Prophylactic Mastectomy among Young Women with Breast Cancer.

Background: There has been an increasing prevalence of contralateral prophylactic mastectomy (CPM), particularly among younger women with breast cancer. There has been limited research evaluating patient preference, knowledge and decision-making regarding this issue. Methods: We surveyed women who had bilateral mastectomy who were enrolled in a multicenter, longitudinal cohort study of women diagnosed with breast cancer at age 40 and younger. The CPM survey included 23 items on decision making, knowledge, and satisfaction with CPM. Results: Of the 550 patients enrolled as of November 2010, 157 (28.5%) had bilateral mastectomy, of whom 124 completed the CPM survey (response rate 79%). Women with bilateral breast cancer (3) or bilateral prophylactic (1) indications for surgery were excluded. Median age at diagnosis was 37 years (range 26–40); 26 women (21%) reported having a genetic mutation (21 BRCA1 and 5 BRCA2). Excluding mutation carriers, women estimated that a median of 10 of 100 women (range 0–90) would develop contralateral breast cancer in the 5 years after unilateral breast cancer treatment and that 5 of 100 women (range 0 — 98) treated with CPM would develop contralateral breast cancer. Eighteen percent of all respondents believed that women who undergo bilateral mastectomy live longer. Women were asked the importance of potential reasons for undergoing CPM (see Table 1). Eighty-two percent of women were “extremely confident” in their decision to undergo CPM and 92% would “definitely” still choose CPM. Conclusion: Young women with breast cancer have high rates of CPM. Many young women who have undergone CPM overestimate the risk of contralateral disease and the benefits of CPM, including believing that CPM will prevent metastasis and extend life. Interventions to counsel young women with early breast cancer to help them make optimal surgical treatment decisions are needed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-10.

First-in-human clinical trials of imaging devices: An example from optical imaging

Clinical translation of scientific discoveries is often the long-term goal of academic medical research. However, this goal is not always realized due to the complicated path between bench research and clinical use. In this review, we outline the fundamental steps required for first-in-human testing of a new imaging device, and use the FLARE™ (Fluorescence-Assisted Resection and Exploration) near-infrared fluorescence optical imaging platform as an example.

Surgical Complications and the Use of Neoadjuvant Bevacizumab.

Introduction:Neoadjuvant chemotherapy is being increasingly used in operable breast cancer. There are limited data on the safety of bevacizumab (Bev) in combination with chemotherapy in the neoadjuvant setting. We sought to explore the safety and efficacy of neoadjuvant cisplatin/Bev in a protocol for triple negative breast cancer (TNBC), with post operative dose dense AC or AC/Taxol plus Bev. We present our operative experience, including postoperative complications. We also compared this to a smaller single arm neoadjuvant cisplatin alone study.Methods:51 patients with confirmed TNBC provided informed consent and were enrolled in a single arm phase II trial of neoadjuvant cisplatin 75 mg/m 2 plus Bev15 mg/kg q 3 weeks x 3 cycles with the 4 th cycle cisplatin alone prior to definitive surgery. This design allowed at least 6 weeks between the last dose of Bev and surgery. Research biopsies were obtained before treatment and at surgery. Postoperatively, patients received doxorubicin and cytoxan (AC) plus bevacizumab or AC/Taxol plus Bev. Median age was 50 yrs (range 30-65 yrs); tumors were clinical stage II 48 (94%) and stage III 3 (6%).28 patients with confirmed TNBC were enrolled in our phase II trial of neoadjuvant cisplatin. Single-agent cisplatin 75mg/m 2 q3weeks x 4cycles was given prior to definitive surgery. Median age was 50 yrs (range 29-69yrs); tumors were clinical stage II (75%), stage III (25%). Postoperatively, patients received AC or AC/Taxol. Two-sided Fisher exact test were used for comparing the 2 trials.Results:Fifty-one patients received neoadjuvant protocol therapy with cisplatin/Bev (all received at least one cycle of bevacizumab, 7 did not complete all cycles of preop bevacizumab) and underwent definitive local therapy to the breast. Breast conserving therapy was performed in 29 (57%) and mastectomy with or without reconstruction in 22 (43%). Postoperative complications were reported in 22 (43%) of patients: 4 (8%) required wound debridement and explantation of expanders, 8 (16%) wound breakdowns, 5 (10%) developed hematomas requiring operative intervention and 5 (10%) seromas requiring multiple aspirations.Twenty-eight patients completed neoadjuvant cisplatin therapy and underwent definitive local therapy to the breast. Breast conserving therapy was performed in 13 (46%) and mastectomy with or without reconstruction in 16 (54%). Postoperative complications were reported in 11 (39%) of patients: 5 seromas requiring drainage (18%), 2 hematomas (7%), 2 abscesses (7%), and 2 (7%) wound breakdowns. No reconstructions were lost including the 3 expanders and 2 TRAM flaps.We compared all toxicities between the two trials, (p= 0.81 NS), and wound healing related complications between the two trials (p= 0.10 NS).Conclusions:Cisplatin/Bevacizumab and cisplatin alone neoadjuvant therapy resulted in a significant number of postoperative complications. Specifically use of expanders or implants may be problematic for patients treated with Bev with a trend towards more wound related events for this group. However, this was a single arm trial, a randomized controlled studies will be necessary in determine the optimal use of bevacizumab in the timing of breast cancer surgery. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 43.

Immediate breast reconstruction following mastectomy in pregnant women with breast cancer

Surgical management of breast cancer in pregnancy (BCP) requires balancing benefits of therapy with potential risks to the developing fetus. Minimal data describe outcomes after mastectomy with immediate breast reconstruction (IR) in pregnant patients.