IntroductionBreast conserving surgery in the setting of ductal carcinoma in situ (DCIS) produces many challenges. Re-excision rates for close or negative margins after lumpectomy are common due to difficulty in intraoperative margin status assessment. The objective of this study was to review our experience with various margin assessment techniques in the setting of a preoperative diagnosis of DCIS on core needle biopsy (CNB).MethodsA prospectively gathered database of surgically-treated breast cancer patients was reviewed for patients with a diagnosis of DCIS as the most significant lesion on CNB from 1997 to 2009. Of 425 patients with a diagnosis of DCIS by CNB, 231 patients underwent a lumpectomy. Patients' age, tumor characteristics, type of surgery, margin assessment technique, and follow up data were recorded.Results231 patients underwent a lumpectomy following a CNB of DCIS. 138 patients (59.7%) had intra-operative touch prep (TP) analysis of all 6 margins, 39 patients (16.9%) underwent intra-operative gross evaluation of margins, 53 (22.9%) patients had no intra-operative analysis, and one patient (0.4%) had a frozen section analysis. Success at achieving negative margins (>2mm) with initial lumpectomy was 66.7% (92/138) for TP analysis, 56.4% (22/39) for gross evaluation, and 52.8% (28/53) for no margin assessment. These percentages did not reach statistical significance by odds ratios (TP to Gross p= 0.24, TP to None p=0.08, Gross to None p=0.73). After excluding patients that required mastectomy following an unsuccessful lumpectomy, ipsilateral breast recurrence rates were 6.3% (8/127) for the touch prep patients after a mean follow up of 4.0 years, 0.0% (0/31) for the gross evaluation patients after a mean follow up of 1.9 years, and 10.5% (4/38) for the patients with no intraoperative assessment after a mean follow up of 3.8 years. Characteristics of each group are listed in Table 1.ConclusionsReexcision for close or positive margins is required for a significant percentage of patients who undergo lumpectomy after a preoperative diagnosis of DCIS on CNB. Although intraoperative TP analysis had the highest success of preventing reexcision, long term data suggest that recurrence rates between intraoperative TP and gross evaluation are both acceptable with short term follow up.Table 1: Characteristics of patients undergoing lumpectomy with a preoperative diagnosis of DCIS on CNBMargin AssessmentTouch PrepGrossNoneFrozenNumber of cases13839531Patient Median Age59.758.956.359.8Cases not needing Reexcision66.7%(92/138)56.4% (22/39)52.8% (28/53)0%(0/1)Cases that received mastectomy8.0%(11/138)20.5%(8/39)26.4%(14/53)100%(1/1)DCIS Grade3- 512- 631- 22Unk- 23- 162- 151- 5Unk- 33-252-201- 7Unk- 13- 02- 01- 1Unk- 0Cases with Necrosis50%(69/138)53.9%(21/39)62.3%(33/53)0%(0/1)Cases upgraded to Invasive Cancer12.3%(17/138)15.4%(6/39)35.9%(19/53)0%(0/1)ReceivedRadiation after lumpectomy85.0%(108/127)67.7% (21/31)76.3%(29/38)0%(0/1)ReceivedTamoxifen after lumpectomy34.7%(44/127)25.8%(8/31)31.2%(12/38)0%(0/1)Ipsilateral breastRecurrence after lumpectomy6.3%(8/127)0%(0/31)10.5% (4/38)0%(0/1)Follow up after lumpectomy (years)4.0(0-10.6)1.9(0.19-5.6)3.8(0.17-9.4)6.0 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4122.
Background: The decision to use adjuvant chemotherapy in patients with early stage breast cancer is based in part on the estimation of risk of tumor recurrence by physicians, which traditionally relies heavily on tumor size, nodal status and a set of biologic tumor characteristics such as hormone receptor and HER2 expression. The Oncotype DX® assay is a 21-gene expression profile aiming to improve risk stratification, recurrence prediction and optimize selection of patients for adjuvant chemotherapy.Methods: We selected 154 consecutive patients with early stage estrogen receptor (ER) positive breast cancer and available Oncotype Dx® recurrence score (RS) for the study. Clinicopathologic data, including patient age, menopausal status, tumor size, histologic type, grade, mitotic activity, presence of lymphatic invasion (LVI), nodal status, hormone receptor and HER2 status on all patients were provided to four surgical oncologists, four medical oncologists and three pathologists, specializing in breast cancer diagnosis and management. Participants were asked to estimate the risk of recurrence of tumors based on available clinicopathologic data and to provide the three most important tumor features their risk estimates were based on. Risk estimates of participants were compared with RS results.Results: Based on the Oncotype Dx® results, 95 (61.7%), 45 (29.2%) and 14 (9.1%) tumors were of low (RS <18), intermediate (RS 18-30) and high (RS ≥31) risk, respectively. RS values showed a highly significant correlation with tumor grade, mitotic activity, LVI, hormone receptor and HER2 status, while no correlation with patient age, menopausal status, tumor size and histologic type was found. Participants' risk estimates agreed with those of the Oncotype Dx® assay in 54.2 ± 2.3 % (mean ± SEM, range 41.6 - 63.0%) of cases, while the risk of recurrence was over- and underestimated compared to RS results in 31.8 ± 3.1% (16.2 - 43.5%) and 14.1 ± 1.4% (7.1 - 22.7%), respectively. The rates of overestimation were significantly higher than those of underestimation (p = 0.0003). Although medical oncologists tended to overestimate the risk more frequently (38.1 ± 2.0%) compared to surgeons (28.7 ± 5.9%) and pathologists (27.5 ± 7.8%), the difference did not reach statistical significance. Estimation of the agreement of participants' risk assessment with RS results showed a mean kappa value of 0.2955 (range 0.1506 - 0.4123). No statistically significant difference in overall concurrence with RS results was found between surgeons, medical oncologists and pathologists. Participants ranked tumor stage/nodal status, hormone receptor status and tumor size to be the most important features when estimating recurrence risk.Conclusions: Based on traditional clinicopathologic features alone, surgeons, medical oncologists and pathologists tend to overestimate the risk of tumor recurrence as compared to Oncotype Dx® assay results. The RS may provide additional information regarding the intrinsic biological features of ER positive breast cancers and help tailoring treatment recommendations. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4061.
Background: Current guidelines recommend administration of chemotherapy for patients with breast carcinomas >1 cm in size, with consideration for patient age, comorbidities and tumor grade. However, it is unknown which patients actually benefit from therapy and overtreatment of a significant proportion of patients is a major concern. We investigated the impact of the Oncotype Dx® Recurrence Score (RS) on chemotherapy recommendations in early stage estrogen receptor (ER) positive breast cancer patients.Methods: We selected 154 patients with early stage ER positive breast cancer and available RS for the study. Clinicopathologic data, including age, menopausal status, tumor size, type, grade, mitotic activity, presence of lymphatic invasion, nodal status, hormone receptor and HER2 status on all patients were provided to four surgical oncologists, four medical oncologists and three pathologists, specializing in breast cancer diagnosis and management. Assuming that all patients were in good general health and would receive endocrine therapy, participants were asked whether they would also advovate adjuvant chemotherapy based on clinicopathologic data with and without knowledge of the RS, and to provide the three salient clinicopathologic features on which their recommendations were based. Changes in recommendations of participants following inclusion of RS data were compared.Results: Based on RS results, 95 (61.7%), 45 (29.2%) and 14 (9.1%) tumors were of low (RS <18), intermediate (RS 18-30) and high (RS ≥31) risk, respectively. The results are summarized in Table 1. Assuming that the hypothesis previously put forward that patients with low to intermediate risk RS are not likely to benefit from chemotherapy, 82.3 ± 1.3% (75.5 - 89.0%) and 69.0 ± 6.9% (5.9 - 85.7%) of patients for whom chemotherapy was recommended by the participants would be "overtreated" without and with the use of RS results (p = 0.0322). No statistically significant difference was found among surgeons, medical oncologists and pathologists. Participants ranked patient age/menopausal status, hormone receptor status and tumor stage/nodal status to be the most important features when recommending chemotherapy.Conclusions: Although current recommendations for adjuvant chemotherapy for early stage ER positive breast cancer patients are largely in line with published guidelines, inclusion of RS alters recommendations in about 25% of cases. While medical oncologists recommended chemotherapy more frequently compared to surgeons and pathologists, they were more likely to change recommendations in light of RS results.Table 1. Summary of results SurgeonsMedical oncologistsPathologistsp* Mean ± SEMRangeMean ± SEMRangeMean ± SEMRange Chemo without RS (%)29.2 ± 1.824.0 - 31.859.0 ± 5.046.8 - 70.846.8 ± 3.741.6 - 53.90.0156Chemo with RS (%)27.0 ± 5.611.0 - 36.438.6 ± 9.517.5 - 63.644.4 ± 5.833.8 - 53.90.1794No change (%)75.3 ± 7.054.5 - 85.766.7 ± 6.851.3 - 83.885.9 ± 6.478.6 - 98.70.3682Add chemo (%)11.2 ± 4.13.2 - 22.76.5 ± 1.93.2 - 11.75.8 ± 3.20.6 - 11.70.6882Avoid chemo (%)13.5 ± 3.94.5 - 22.726.8 ± 7.94.5 - 41.68.2 ± 4.50.6 - 16.20.2186*Kruskal-Wallis test Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4058.
Backround: Autologous intratumoral dendritic cell injections were used to modulate the tumor reduction effects of standard neoadjuvant chemotherapy. Dendritic cells are important in the regulation of T cell immunity and have been shown to have activity in cancer patients. The neoadjuavant combination therapy was designed to expose dendritic cells to tumor cell apoptosis leading to induction of tumor antigen-specific responses.Methods: Seventeen women with stage II or III breast cancer with breast tumors at least 3 cm in size and had a confirmed initial breast biopsy were entered into this trial from August 2007 through 2009. All patients participating in the clinical trial had tumors that expressed either carcinoembryonic antigen (CEA) or survivin and were HER2-neu negative. They received 4 cycles of paclitaxel at 175 mg/m2 followed by 4 cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) in a bi-weekly dose dense fashion. Pegfilgrastim 6 mg subcutaneous injection was administered 24 hours after each cycle of chemotherapy. Autologous intratumoral dendritic cell injections were administered one week following the first three paclitaxel treatments. All patients consented to a pre-treatment biopsy and a second tumor biopsy after 4 cycles of paclitaxel to evaluate responses to the intratumoral dendritic cell injections. The endpoints of this trial included assessment of clinical and pathologic response in the breast, safety of the intratumoral dendritic cell injection, evaluation of tumor response, and induction of T cell responses to tumor antigens.Results: Fourteen patients are evaluable for response. The median age was 51.5, the median tumor size was 5.6 cm, and 64 % were estrogen receptor positive. A complete clinical response was observed in 57%, a partial response in 36%, and one stable disease response. A pathologic complete response with no evidence of tumor in the breast was confirmed in 2 patients (14 %). Treatment was well tolerated with no incidence of toxicity observed related to the intratumoral dendritic cell injections. Grade 3/4 hematologic toxicity was as expected for the chemotherapy. Other grade 3/4 toxicity related to the chemotherapy included fatigue, hand-foot, infection, mucositis, and hypocalcemia.Discussion: Combination neoadjuvant therapy with dose-dense paclitaxel followed by AC and autologous intratumoral dendritic cell injections administered between the first three cycles of paclitaxel is safe with no toxicity observed related to the intratumoral dendritic cell injections. Immune response to the treatment is being evaluated by proliferation and interferon-gamma production by peripheral blood mononuclear cells in response to tumor cell lysates, survivin, and CEA. Initial evaluation indicates that treatment resulted in generation of tumor specific responses in more than half of all treated patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4128.
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