Deborah Axelrod

Topical TLR7 Agonist Imiquimod Can Induce Immune-Mediated Rejection of Skin Metastases in Patients with Breast Cancer

Purpose: Skin metastases of breast cancer remain a therapeutic challenge. Toll-like receptor 7 agonist imiquimod is an immune response modifier and can induce immune-mediated rejection of primary skin malignancies when topically applied. Here we tested the hypothesis that topical imiquimod stimulates local antitumor immunity and induces the regression of breast cancer skin metastases. Experimental Design: A prospective clinical trial was designed to evaluate the local tumor response rate of breast cancer skin metastases treated with topical imiquimod, applied 5 d/wk for 8 weeks. Safety and immunologic correlates were secondary objectives. Results: Ten patients were enrolled and completed the study. Imiquimod treatment was well tolerated, with only grade 1 to 2 transient local and systemic side effects consistent with imiquimods immunomodulatory effects. Two patients achieved a partial response [20%; 95% confidence interval (CI), 3%–56%]. Responders showed histologic tumor regression with evidence of an immune-mediated response, showed by changes in the tumor lymphocytic infiltrate and locally produced cytokines. Conclusion: Topical imiquimod is a beneficial treatment modality for breast cancer metastatic to skin/chest wall and is well tolerated. Importantly, imiquimod can promote a proimmunogenic tumor microenvironment in breast cancer. Preclinical data generated by our group suggest superior results with a combination of imiquimod and ionizing radiation and we are currently testing in patients whether the combination can further improve antitumor immune and clinical responses. Clin Cancer Res; 18(24); 6748–57. ©2012 AACR.

Is Surgical Excision Necessary for the Management of Atypical Lobular Hyperplasia and Lobular Carcinoma In Situ Diagnosed on Core Needle Biopsy?: A Report of 38 Cases and Review of the Literature

CONTEXT Both atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) have traditionally been considered to be risk factors for the development of invasive carcinoma and are followed by close observation. Recent studies have suggested that these lesions may represent true precursors with progression to invasive carcinoma. Due to the debate over the significance of these lesions and the small number of cases reported in the literature, the treatment for lobular neoplasia diagnosed by percutaneous core biopsy (PCB) remains controversial. OBJECTIVE To review our experience with pure LCIS or ALH diagnosed by PCB and correlate the radiologic findings and surgical excision diagnoses to develop management guidelines for lobular neoplasia diagnosed by PCB. DESIGN We searched the pathology database for patients who underwent PCB with a diagnosis of either pure LCIS or ALH and had subsequent surgical excision. We compared the core diagnoses with the surgical excision diagnoses and the radiologic findings. RESULTS Thirty-eight PCBs with a diagnosis of ALH (18 cases) or LCIS (20 cases) were identified. Carcinoma was present at excision in 1 (6%) of the ALH cases and in 2 (10%) of the LCIS cases. In summary, 8% (3/38) of PCBs diagnosed as lobular neoplasia (ALH or LCIS) were upgraded to carcinoma (invasive carcinoma or ductal carcinoma in situ) at excision. CONCLUSIONS Surgical excision is indicated for all PCBs diagnosed as ALH or LCIS, as a significant percentage will show carcinoma at excision.

Acute toxicity of high-dose-rate intracavitary brachytherapy with the MammoSite applicator in patients with early-stage breast cancer.

Background: Intracavitary brachytherapy with the MammoSite applicator as the sole radiation treatment in breast-conserving therapy is an option for women with early-stage breast cancer; we evaluated the acute toxicities associated with this treatment method.Methods: Thirty-one patients with 32 stage I or II breast carcinomas underwent breast-conserving therapy, which included lumpectomy with negative margins, sentinel node biopsy, or axillary dissection, followed by brachytherapy with the MammoSite applicator. Acute radiation skin complications were graded on the day of radiotherapy completion and at weeks 2, 4, 6, and 12 after radiation treatment. Cosmesis was graded on the Harvard Scale at all follow-ups.Results: The median follow-up was 11 months (range, 4–15 months). Twenty-seven of the 31 patients were treated with the device as the sole method of radiotherapy. No acute toxicities occurred during the 5 days of treatment. Nineteen patients (68%) had no to mild acute skin reactions, and 25% developed bright erythema and patchy moist desquamation. Two patients (7%) developed confluent moist desquamation within the first 4 weeks (grade 3); this healed by week 12. All skin reactions were localized to the area overlying the balloon. Sixteen percent (5 of 32) of all breasts with implants developed infection. Cosmesis was good to excellent in 86% of cases.Conclusions: Most acute skin toxicities were mild. Our infection rate was higher than in prior studies that used interstitial brachytherapy. Cosmesis was good to excellent in most patients. Breast brachytherapy with the MammoSite catheter was well tolerated; further investigations of breast brachytherapy with this system are warranted.

Evaluation of Aromatherapy in Treating Postoperative Pain: Pilot Study

Abstract:  This study compared the analgesic efficacy of postoperative lavender oil aromatherapy in 50 patients undergoing breast biopsy surgery. Twenty‐five patients received supplemental oxygen through a face mask with two drops of 2% lavender oil postoperatively. The remainder of the patients received supplemental oxygen through a face mask with no lavender oil. Outcome variables included pain scores (a numeric rating scale from 0 to 10) at 5, 30, and 60 minutes postoperatively, narcotic requirements in the postanesthesia care unit (PACU), patient satisfaction with pain control, as well as time to discharge from the PACU. There were no significant differences in narcotic requirements and recovery room discharge times between the two groups. Postoperative lavender oil aromatherapy did not significantly affect pain scores. However, patients in the lavender group reported a higher satisfaction rate with pain control than patients in the control group (P = 0.0001).

The effect of providing information about lymphedema on the cognitive and symptom outcomes of breast cancer survivors.

Despite recent advances in breast cancer treatment, breast cancer related lymphedema (BCRL) continues to be a significant problem for many survivors. Some BCRL risk factors may be largely unavoidable, such as mastectomy, axillary lymph node dissection (ALND), or radiation therapy. Potentially avoidable risk factors unrelated to breast cancer treatment include minor upper extremity infections, injury or trauma to the arm, overuse of the limb, and air travel. This study investigates how providing information about BCRL affects the cognitive and symptomatic outcome of breast cancer survivors. Data were collected from 136 breast cancer survivors using a Demographic and Medical Information interview instrument, a Lymphedema Education Status interview instrument, a Knowledge Test for cognitive outcome, and the Lymphedema and Breast Cancer Questionnaire for symptom outcome. Data analysis included descriptive statistics, t tests, chi-square (χ2) tests, and regression. BCRL information was given to 57% of subjects during treatment. The mean number of lymphedema-related symptoms was 3 symptoms. Patients who received information reported significantly fewer symptoms and scored significantly higher in the knowledge test. After controlling for confounding factors, patient education remains an additional predictor of BCRL outcome. Significantly fewer women who received information about BCRL reported swelling, heaviness, impaired shoulder mobility, seroma formation, and breast swelling. Breast cancer survivors who received information about BCRL had significantly reduced symptoms and increased knowledge about BCRL. In clinical practice, breast cancer survivors should be engaged in supportive dialogues so they can be educated about ways to reduce their risk of developing BCRL.BackgroundDespite recent advances in breast cancer treatment, breast cancer related lymphedema (BCRL) continues to be a significant problem for many survivors. Some BCRL risk factors may be largely unavoidable, such as mastectomy, axillary lymph node dissection (ALND), or radiation therapy. Potentially avoidable risk factors unrelated to breast cancer treatment include minor upper extremity infections, injury or trauma to the arm, overuse of the limb, and air travel. This study investigates how providing information about BCRL affects the cognitive and symptomatic outcome of breast cancer survivors.MethodsData were collected from 136 breast cancer survivors using a Demographic and Medical Information interview instrument, a Lymphedema Education Status interview instrument, a Knowledge Test for cognitive outcome, and the Lymphedema and Breast Cancer Questionnaire for symptom outcome. Data analysis included descriptive statistics, t tests, chi-square (χ2) tests, and regression.ResultsBCRL information was given to 57% of subjects during treatment. The mean number of lymphedema-related symptoms was 3 symptoms. Patients who received information reported significantly fewer symptoms and scored significantly higher in the knowledge test. After controlling for confounding factors, patient education remains an additional predictor of BCRL outcome. Significantly fewer women who received information about BCRL reported swelling, heaviness, impaired shoulder mobility, seroma formation, and breast swelling.ConclusionsBreast cancer survivors who received information about BCRL had significantly reduced symptoms and increased knowledge about BCRL. In clinical practice, breast cancer survivors should be engaged in supportive dialogues so they can be educated about ways to reduce their risk of developing BCRL.

Papillary lesions of the breast diagnosed by core needle biopsy: 71 cases with surgical follow-up

BACKGROUND Papillary breast lesions comprise a spectrum of histopathologic diagnoses ranging from benign papillomas to papillary carcinomas. There is ongoing controversy regarding the management of papillary lesions diagnosed by core needle biopsy (CNB). Some authors advocate observation of papillary lesions when the CNB is benign, while others recommend surgical excision of all papillary lesions. The current study assessed the adequacy of CNB in evaluating papillary breast lesions. METHODS A search of the pathology database at our institution identified 122 papillary lesions diagnosed by CNB. The study population consisted of 71 papillary lesions that were subsequently surgically excised. RESULTS Of the 71 papillary lesions excised, 8 were malignant, 16 were atypical, and 47 were benign at the time of CNB. Of the 47 papillary lesions thought to be benign, 13 (28%) revealed atypia and 4 (9%) revealed malignancy upon surgical excision. Of the 13 atypical papillary lesions on CNB, 7 lesions (54%) were associated with malignancy upon excision. Slightly over half the upgrades were due to finding atypia or malignancy in the tissue surrounding the papillary lesion. The total rate of upgrades from the CNB diagnosis to the excisional diagnosis was 38%. CONCLUSIONS When a core biopsy of a papillary lesion is encountered, there is a strong likelihood of discovering atypia or malignancy in the index lesion or in close proximity. Therefore, surgical excision should be performed to avoid missing a malignancy and to allow for accurate breast cancer risk assessment that can impact survival and decisions regarding chemoprevention.

Alternative lymphatic pathway after previous axillary node dissection in recurrent/primary breast cancer.

Objectives: The sentinel lymph node approach has almost become the standard procedure of choice in the management of patients with early breast cancer. The status of sentinel nodes, whether or not pathologically involved by cancer cells, represents those of the axillary nodes with a negative predictive value of almost 100%. If the axillary lymphatic nodal drainage is altered, alternative lymphatic pathways and accordingly sentinel node location will be changed. Methods: In this article, 4 patients are presented, 3 with recurrent breast cancer who had already undergone lumpectomy, axillary node dissection, and radiotherapy in the past and 1 with primary breast cancer after surgical removal of a malignant melanoma on her back and had axillary node dissection on the same side as the breast cancer. These patients underwent lymphoscintigraphy followed by sentinel node localization using the gamma probe and also blue dye injection during surgery. Results: All patients showed alternate lymphatic pathways, 1 had an ipsilateral internal mammary node and crossed lymphatics to a contralateral axillary node, 2 had intramammary sentinel nodes, and 1 had an internal mammary on the same side. Pathologic examination of the intramammary and contralateral sentinel nodes were negative for metastases. Internal mammary sentinel nodes were not biopsied. Conclusion: We feel that sentinel node lymphoscintigraphy should be done even in patients who have altered lymphatic pathways resulting from previous axillary node dissection. It allows identifying and biopsy of the sentinel node at its new unpredicted location.

“Hormesis”—An Inappropriate Extrapolation from the Specific to the Universal

Abstract Although it is generally accepted that some chemicals may have beneficial effects af low doses, incorporating these effects into risk assessments generally ignores well-established factors related to exposure and human susceptibility. The authors argue against indiscriminate application of hormesis in assessments of chemical risks for regulatory purposes.

The lateral inframammary fold incision for nipple-sparing mastectomy: outcomes from over 50 immediate implant-based breast reconstructions.

Nipple‐sparing mastectomy (NSM) as a therapeutic or prophylactic procedure for breast cancer is rapidly gaining popularity as the literature continues to support it safety. The lateral inframammary fold (IMF) approach provides adequate exposure and eliminates visible scars on the anterior surface of the breast, making this incision cosmetically superior to radial or periareolar approaches. We reviewed 55 consecutive NSMs performed through a lateral IMF incision with immediate implant‐based reconstruction, with or without tissue expansion, between June 2008 and June 2011. Prior to incision, breasts were lightly infiltrated with dilute anesthetic solution with epinephrine. Sharp dissection, rather than electrocautery, was used as much as possible to minimize thermal injury to the mastectomy flap. When indicated, acellular dermal matrix was placed as an inferolateral sling. Subsequent fat grafting to correct contour deformities was performed in select patients. Three‐dimensional (3D) photographs assessed changes in volume, antero‐posterior projection, and ptosis. Mean patient age was 46 years, and mean follow‐up time was 12 months. Twelve mastectomies (22%) were therapeutic, and the remaining 43 (78%) were prophylactic. Seven of the nine sentinel lymph node biopsies (including one axillary dissection) (78%) were performed through the lateral IMF incision without the need for a counter‐incision. Acellular dermal matrix was used in 34 (62%) breasts. Average permanent implant volume was 416 cc (range 176–750 cc), and average fat grafting volume was 86 cc (range 10–177 cc). In one patient a positive intraoperative subareolar biopsy necessitated resection of the nipple‐areola complex (NAC), and in two other patients NAC resection was performed at a subsequent procedure based on the final pathology report. Mastectomy flap necrosis, requiring operative debridement, occurred in two breasts (4%), both in the same patient. One of these breasts required a salvage latissimus dorsi myocutaneous flap to complete the reconstruction. Three nipples (6%) required office debridement for partial necrosis and operative reconstruction later. No patient had complete nipple necrosis. No statistically significant differences existed between therapeutic and prophylactic mastectomies for developing partial skin and/or nipple necrosis (p = 0.35). Three episodes (5%) of cellulitis occurred, which responded to antibiotics without the need for explantation. Morphological outcomes using 3D scan measurements showed reconstructed breasts were larger, more projected, and less ptotic than the preoperative breasts (196 versus 248 cc, 80 versus 90 mm, 146 versus 134 mm, p < 0.01 for each parameter). Excellent results can be achieved with immediate implant‐based reconstruction of NSM through a lateral IMF incision. NAC survival is reliable, and complication rates are low.

The incidence of positive margins with breast conserving therapy following mammotome biopsy for microcalcification.

The ability to achieve clean margins with breast conserving therapy varies greatly even when the diagnosis of carcinoma is known beforehand. Although several reports reveal that the incidence of positive margins decreases after stereotaxic core biopsy of nonpalpable lesions and fine‐needle aspiration biopsy of palpable lesions, the data on the results following mammotome biopsy (mmbx) is scanty.