Rache M. Simmons

Local and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies.

BACKGROUND Skin-sparing mastectomies (SSMs) are being used more frequently to treat many cases of breast cancer. This type of surgery maximizes breast skin preservation and facilitates immediate reconstruction, resulting in a superior cosmetic appearance after mastectomy and a more satisfied patient. Although SSMs are becoming more common, there are few data regarding the local and distant recurrence rates. METHODS A total of 231 patients treated with mastectomies from 1990 to 1998 were studied, including 77 SSM and 154 non-skin-sparing (NSSM) mastectomy patients. RESULTS The local recurrence rates for SSM and NSSM were 3.90% (3 of 77 patients) and 3.25% (5 of 154 patients), respectively. The local recurrence-free survival at 5 years was 95.3% for SSM patients and 95.2% for NSSM patients (P = .28). The distant recurrence rates of SSM and NSSM were 3.9% (3 of 77 patients) and 3.9% (6 of 154 patients), respectively. The distant recurrence-free actuarial survival at 5 years was 90.2% for SSM patients and 92% for NSSM patients (P = .07). CONCLUSIONS Mastectomies using the skin-sparing technique do not appear to result in any increase in local or distant recurrence and improve aesthetic results of the immediate reconstruction.

Analysis of nipple/areolar involvement with mastectomy: Can the areola be preserved?

Skin-sparing mastectomy (SSM), which involves the resection of the nipple/areolar complex with the breast parenchyma, improves the aesthetic outcome for breast cancer patients. Most patients undergoing SSM desire reconstruction of the nipple/areolar complex for symmetry. These data explore the possibility of preserving the areola in selected mastectomy patients. A retrospective analysis of 217 mastectomy patients was conducted to determine the frequency of malignant nipple and/or areola involvement. The association between nipple and/or areola involvement and prognostic factors, including tumor size, stage, nuclear grade, axillary nodal status, and tumor location, was evaluated. The overall frequency of malignant nipple involvement was 23 of 217 (10.6%). In a subgroup of patients with tumors <2 cm, peripheral tumors, and with two positive nodes or less, the incidence of nipple involvement was 6.7%. When the nipple and areolar involvement were analyzed separately, only 2 of 217 patients had involvement of the areola (0.9%). All patients with areolar involvement had stage 3 breast cancer and were located centrally in the breast. We conclude from these data that nipple preservation is not a reasonable option for mastectomy patients. However, preservation of the areola with mastectomy in selected patients warrants further study.BackgroundSkin-sparing mastectomy (SSM), which involves the resection of the nipple/areolar complex with the breast parenchyma, improves the aesthetic outcome for breast cancer patients. Most patients undergoing SSM desire reconstruction of the nipple/areolar complex for symmetry. These data explore the possibility of preserving the areola in selected mastectomy patients.MethodsA retrospective analysis of 217 mastectomy patients was conducted to determine the frequency of malignant nipple and/or areola involvement. The association between nipple and/or areola involvement and prognostic factors, including tumor size, stage, nuclear grade, axillary nodal status, and tumor location, was evaluated.ResultsThe overall frequency of malignant nipple involvement was 23 of 217 (10.6%). In a subgroup of patients with tumors <2 cm, peripheral tumors, and with two positive nodes or less, the incidence of nipple involvement was 6.7%. When the nipple and areolar involvement were analyzed separately, only 2 of 217 patients had involvement of the areola (0.9%). All patients with areolar involvement had stage 3 breast cancer and were located centrally in the breast.ConclusionsWe conclude from these data that nipple preservation is not a reasonable option for mastectomy patients. However, preservation of the areola with mastectomy in selected patients warrants further study.

Effectiveness of a noninvasive digital infrared thermal imaging system in the detection of breast cancer

BACKGROUND Digital infrared thermal imaging (DITI) has resurfaced in this era of modernized computer technology. Its role in the detection of breast cancer is evaluated. METHODS In this prospective clinical trial, 92 patients for whom a breast biopsy was recommended based on prior mammogram or ultrasound underwent DITI. Three scores were generated: an overall risk score in the screening mode, a clinical score based on patient information, and a third assessment by artificial neural network. RESULTS Sixty of 94 biopsies were malignant and 34 were benign. DITI identified 58 of 60 malignancies, with 97% sensitivity, 44% specificity, and 82% negative predictive value depending on the mode used. Compared to an overall risk score of 0, a score of 3 or greater was significantly more likely to be associated with malignancy (30% vs 90%, P < .03). CONCLUSION DITI is a valuable adjunct to mammography and ultrasound, especially in women with dense breast parenchyma.

Cryoablation of early-stage breast cancer: Work-in-progress report of a multi-institutional trial

BackgroundWith recent improvements in breast imaging, our ability to identify small breast tumors has markedly improved, prompting significant interest in the use of ablation without surgical excision to treat early-stage breast cancer. We conducted a multi-institutional pilot safety study of cryoablation in the treatment of primary breast carcinomas.MethodsTwenty-nine patients with ultrasound-visible primary invasive breast cancer ≤2.0 cm were enrolled. Twenty-seven (93%) successfully underwent ultrasound-guided cryoablation with a tabletop argon gas-based cryoablation system with a double freeze/thaw cycle. Standard surgical resection was performed 1 to 4 weeks after cryoablation. Patients were monitored for complications, and pathology data were used to assess efficacy.ResultsCryoablation was successfully performed in an office-based setting with only local anesthesia. There were no complications to the procedure or postprocedural pain requiring narcotic pain medications. Cryoablation successfully destroyed 100% of cancers <1.0 cm. For tumors between 1.0 and 1.5 cm, this success rate was achieved only in patients with invasive ductal carcinoma without a significant ductal carcinoma-in-situ (DCIS) component. For unselected tumors >1.5 cm, cryoablation was not reliable with this technique. Patients with noncalcified DCIS were the cause of most cryoablation failures.ConclusionsCryoablation is a safe and well-tolerated office-based procedure for the ablation of early-stage breast cancer. At this time, cryoablation should be limited to patients with invasive ductal carcinoma ≤1.5 cm and with <25% DCIS in the core biopsy. A multicenter phase II clinical trial is planned.

Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients.

BACKGROUND Axillary lymph node metastasis (ALNM) represents the single most important prognostic indicator in patients diagnosed with breast cancer. The proportion of < or = 1-cm (T1a, T1b) invasive breast carcinomas is increasing. The incidence and predictive factors associated with ALNM in patients with < or = 1-cm tumors remains unclear and the role of axillary lymph node dissection in these patients has been questioned. The purpose of this study was to determine clinical and pathologic factors predictive of ALNM in patients with < or = 1-cm invasive breast carcinomas by univariate and multivariate analyses. STUDY DESIGN Review analysis from a prospective database identified patients with < or = 1-cm invasive breast cancers treated at our institution between 1990 and 1996. All patients underwent a resection of the primary tumor and axillary lymph node dissections. Routine patient and tumor characteristics evaluated included: age, race, tumor size, histologic grade, estrogen and progesterone receptor status, and lymphatic and vascular invasion. Univariate and multivariate analyses were performed. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are presented. RESULTS A total of 919 patients were identified in this study with tumors < or = 1 cm. These included 199 patients (21.7%) with T1a tumors and 720 patients (78.3%) with T1b tumors. ALNM was detected in 165 patients with an overall incidence of 18.0%. Of the ALNM group, 32 patients (19.4%) had T1a tumors and 133 patients (80.6%) had T1b tumors. Four variables were found to be significant in univariate analysis. These included: increasing tumor size, poor histologic grade, presence of lymphatic or vascular invasion, and younger age of the patient. An increase in tumor size was associated with a significant risk of ALNM (OR = 2.66, 95% CI = 1.28 to 5.75; p = 0.01). Poor tumor grade and the presence of lymphatic or vascular invasion were also associated with an increased risk of ALNM (OR = 2.69, p = 0.003 and OR = 5.52, p = 0.0001, respectively). Patients with ALNM were more likely to have a tumor grade of 3 (25.0% ALNM versus 12.5% node-negative, p = 0.004) and lymphatic or vascular invasion (16.9% ALNM versus 3.5% node-negative, p < 0.0001). In multivariate analysis, an increased risk of ALNM was demonstrated with increasing tumor size (0.1-cm increments), poor histologic grade, and younger age. CONCLUSIONS This study investigated clinical and pathologic factors influencing ALNM in patients with T1a and T1b breast carcinomas. We have identified three factors by multivariate analysis as significant independent predictors of ALNM in this group of patients. These include increasing tumor size, poor histologic grade, and younger age. Given the significant amount of ALNM demonstrated in this study (overall 18%) and the inability to identify a subgroup of patients that had an acceptable low risk of ALNM, the complete omission of assessing the axilla for metastatic disease in patients with small breast cancers cannot be advocated. Our recommendation for patients diagnosed with T1a and T1b tumors is to have their axilla investigated for metastatic disease either by traditional axillary lymph node dissections or by intraoperative lymphatic mapping and sentinel lymph node biopsy techniques.

Fibrin sealant reduces the duration and amount of fluid drainage after axillary dissection: a randomized prospective clinical trial.

BACKGROUND Patients who have axillary dissections during lumpectomy or modified radical mastectomy for breast carcinoma accumulate serosanguinous fluid, potentially resulting in a seroma. Currently accepted practice includes insertion of one or more drains for fluid evacuation. This multicenter, randomized, controlled, phase II study was undertaken to evaluate whether a virally inactivated, investigational fibrin sealant is safe and effective when used as a sealing agent to reduce the duration and volume of serosanguinous fluid drainage and to determine the dose response of this effect. STUDY DESIGN Patients undergoing lumpectomy or modified radical mastectomy were randomized to treatment with 4, 8, or 16 mL of fibrin sealant or control (no agent) at the axillary dissections site. Patients undergoing modified radical mastectomy also received an additional 4 or 8 mL of fibrin sealant at the skin flap site. Efficacy was evaluated by the number of days required for wound drainage and the volume of fluid drainage compared with control. Safety was confirmed by clinical course, the absence of viral seroconversion, and no major complications attributable to the sealant. RESULTS The 4-mL axillary dissection dose of fibrin sealant significantly reduced the duration and quantity of fluid drainage from the axilla following lumpectomy (p < or = 0.05). In the modified radical mastectomy patients, a 16-mL axillary dissection dose combined with an 8-mL skin flap dose was significantly effective in reducing the number of days to drain removal (p < or = 0.05) and fluid drainage (p < or = 0.01). There were no fibrin sealant patient viral seroconversions and no major complications attributable to the sealant. A number of wound infections were noted, although this may represent a center-specific effect. CONCLUSIONS Application of fibrin sealant following axillary dissection at the time of lumpectomy or modified radical mastectomy can significantly decrease the duration and quantity of serosanguinous drainage. The viral safety of the product was also supported.

Factors Associated With Residual Breast Cancer After Re-excision for Close or Positive Margins

Background: Successful breast conservation surgery (BCS) requires complete tumor excision. Margin status of the initial specimen determines the need for additional surgery. We explored factors associated with residual cancer (RC) upon follow-up surgery in patients with close, positive, or undetermined margins following BCS.Methods: A retrospective analysis of 276 patients with initial close, positive, or undetermined margins who underwent re-excision (RE) or mastectomy was conducted. All initial excisions were intended as definitive procedures. Chi-square analysis was used to identify factors that may predict RC.Results: Of 276 patients, 87 had close, 168 had positive, and 21 had undetermined margins on initial excision. Of this group, 63% (175/276) had RC upon RE or mastectomy. Of positive-margin patients, 68% had RC, compared with 53% of close-margin and 67% of undetermined-margin patients (P = .006). Tumors ≥2 cm were more often associated with RC than smaller tumors (70.8% vs. 56.5%; P = .07). This association was strongest in positive-margin patients (P = .04). High tumor grade was associated with RC in all groups. RC linearly increased with the number of involved margins (P = .02). Specimen inking with multiple colors was associated with decreased risk of RC (P = .004).Conclusions: Over half of patients with involved or undetermined margins had RC upon RE or mastectomy. Positive and undetermined margins were more often associated with RC than close margins. Larger tumor size was associated with RC in patients with positive. Increasing tumor grade suggests a greater chance of detecting RC in all groups. Multiple involved margins led to a greater risk of RC.

Novel Intraoperative Molecular Test for Sentinel Lymph Node Metastases in Patients With Early-Stage Breast Cancer

PURPOSE An accurate, intraoperative sentinel lymph node (SLN) test could decrease delayed axillary dissections. Molecular tests may be more sensitive than current intraoperative tests but historically have not been rapid enough and have not been properly validated. We present the results from a large, prospective evaluation of the first rapid molecular SLN test, the Breast Lymph Node (BLN) Assay. METHODS A beta trial (n = 304) to determine the threshold levels of mammaglobin and cytokeratin 19 correlating with metastasis greater than 0.2 mm and a validation trial (n = 416) to validate the threshold cutoffs were conducted. Alternating portions from each SLN were processed for histology and the BLN Assay. RESULTS BLN Assay performance against extensive permanent-section histology verified by central pathology review was similar to that expected of standard permanent-section histology: sensitivity, 87.6%; specificity, 94.2%; positive predictive value, 86.2%; and negative predictive value (NPV), 94.9%. In 319 patients with both frozen-section hematoxylin and eosin results and BLN Assay results, the BLN Assay had higher sensitivity (95.6%) and NPV (98.2%) than frozen section (sensitivity, 85.6%; NPV, 94.5%). The assay can be performed in approximately 36 to 46 minutes for one to three nodes. CONCLUSION The BLN Assay allows a rapid evaluation of 50% of each SLN. Comparison with permanent-section histology on adjacent node pieces evaluated by expert pathologists indicated that the BLN Assay was more sensitive than current intraoperative techniques while maintaining high specificity. These data indicate that the assay may be clinically useful for intraoperative or postoperative axillary lymph node dissection decisions.

Radiofrequency ablation of early-stage invasive breast tumors: an overview.

As the management of breast cancer evolves toward less invasive treatments, the next step is the possibility of removing the primary tumor without surgery. The most promising of the noninvasive ablation techniques is radiofrequency ablation, which uses frictional heating that is caused when ions in the tissue attempt to follow the changing directions of a high-frequency alternating current. Three pilot studies, including an ongoing study at M.D. Anderson Cancer Center, have demonstrated that radiofrequency ablation is effective for the destruction of small primary breast cancers. The most important factorfor successful radiofrequency ablation is accuracy of the ultrasound evaluation, which is used to estimate tumor size, localize the tumor for treatment, and monitor the progress of the ablation. A study in preparation at M.D. Anderson will determine whether the use of radiofrequency ablation alone for the local treatment of primary breast cancer will result in outcomes equivalent to those obtained with breast conservation therapy.

Ductal carcinoma in situ with microinvasion

BACKGROUND Ductal carcinoma in situ (DCIS) accounts for nearly 20% of new breast cancer diagnoses and ductal carcinoma in situ with microinvasion (DCIS-MI) is found in 5% to 10% of DCIS. Controversy exists regarding the appropriate local treatment as well as whether or not examination of the axilla should be performed either by sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND) or not at all. METHODS A MEDLINE search was performed using the keywords ductal carcinoma in situ and microinvasion. Recent articles pertaining to the definition and characterization of DCIS-MI as well as treatment and prognosis were analyzed. CONCLUSIONS The data at this time demonstrate no survival benefit for patients undergoing mastectomy versus lumpectomy and radiation. Numerous studies demonstrate axillary lymph node involvement to be as high as 20% with DCIS-MI; therefore, we believe that axillary sampling is essential. We recommend SLNB, which is accurate, provides information necessary for staging and treatment, and is associated with less morbidity than traditional ALND.