Exploring Racial Differences in Treatment Decision-making in Chinese Immigrant and White American Breast Cancer Patients: the Role of Patient-Provider Communication.

Chinese immigrant cancer patients report suboptimal patient-provider communication, which increases the likelihood of decisional conflict and unsatisfactory treatment decision-making (TDM) outcomes (e.g., low satisfaction and perceived control over cancer care). This cross-sectional study explored whether (1) communication and decisional conflict factors associated with TDM outcomes differed between Chinese immigrant and non-Hispanic White breast cancer patients, and (2) the association between patient-provider communication and the outcomes were mediated by TDM factors, regardless of race. Ninety-eight breast cancer patients, diagnosed at stage I-III participated in cross-sectional survey interviews. TDM outcomes and possible predictors of the outcomes (e.g., patient-provider communication, decisional conflict, preference for who makes the treatment decision) were assessed. Linear regression and mediational testing were performed to examine associations among variables of interest. Of the 98, 85 were included for analysis. Chinese patients with limited English proficiency (n = 37) had poorer patient-provider communication, higher decisional conflict, and preferred providers to make decisions than non-Hispanic White patients (n = 48; all p < .05). They also had lower satisfaction with their TDM process after controlling for predictors (e.g., patient-provider communication) (p < .001). There were no significant racial differences in perceived control, controlling for covariates. Regardless of race, patients who reported quality patient-provider communication reported less decisional conflict. These patients also reported increased satisfaction and perceived control. The disparities Chinese immigrant cancer patients experienced in the TDM process may be related to their cultural communication style with providers. Facilitating Chinese patients' communication and partnership with providers may reduce decisional conflicts and increase their TDM outcomes.

Use of MarginProbe as an adjunct to standard operating procedure does not significantly reduce re-excision rates in breast conserving surgery.

PURPOSE: A positive margin after breast conserving surgery has consistently been shown to be a significant predictor for ipsilateral breast tumor recurrence. Currently, there is no standard for intraoperative margin assessment during lumpectomy, and up to 20% of cases result in positive margins. MarginProbe is a device that provides real-time evaluation of lumpectomy margins during surgery. The aim of this study was to evaluate the impact of MarginProbe as an adjunct to standard operating procedure (SOP). METHODS: Patients diagnosed with breast cancer scheduled for breast conserving surgery were consented for intraoperative use of MarginProbe. Shaved margins were excised based on margin assessment using the surgeon's SOP which included specimen radiography and gross pathologic examination, and feedback from the device. The primary endpoint was re-excision rate. Secondary endpoints included sensitivity, specificity, false-positive and negative rates. RESULTS: Of the 60 breast cancers, initial histologically close/positive margins were identified in 18 patients (30%). The re-excision rate in the overall cohort was 6.6%, compared to a historical re-excision rate of 8.6% (p < 0.01). Based on 360 measurement sites, MarginProbe demonstrated a sensitivity of 67% and specificity of 60%, with a positive predictive value of 16%, and of negative predictive value of 94%, which was similar to the accuracy of SOP. CONCLUSIONS: MarginProbe performs equally as well as specimen radiography and gross pathologic examination. In this setting where the baseline re-excision rate was low, the use of MarginProbe as an adjunct to SOP resulted in a small 2% absolute reduction in re-excision rate.

Association of reactive oxygen species levels and radioresistance in cancer stem cells.

The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.

Skin-sparing mastectomy: a survey based approach to defining standard of care.

Skin-sparing mastectomy (SSM) followed by immediate reconstruction has been advocated as an effective treatment option for patients with early-stage breast carcinoma. It markedly improves the quality of breast reconstruction through preservation of the natural skin envelope and a smaller incision. The purpose of this study was to investigate general surgeons' attitudes towards SSM. A postal questionnaire survey of California general surgeons was conducted regarding SSM. Of 370 respondents who stated they performed breast cancer surgery, 331 perform mastectomy for cancer with planned immediate reconstruction. Ninety per cent of respondents did not feel that SSM resulted in higher rates of local recurrence. In addition, 70 per cent felt that the cosmetic results of immediate breast reconstruction after SSM were better than those after a standard mastectomy. Despite this, only 61 per cent perform SSM in most cases when immediate breast reconstruction is planned. The majority of general surgeons perform SSM and therefore it should be considered standard of care. Despite a growing body of literature demonstrating high rates of patient satisfaction and long-term oncologic safety with SSM, there remains significant variation in practice patterns among general surgeons. Additional effort in general surgery education regarding the feasibility and safety of SSM is needed.

Male breast cancer 15 years after allogeneic hematopoietic cell transplantation including total body irradiation for recurrent acute lymphoblastic leukemia.

BACKGROUND: Over the years, the prognosis following treatment of a primary cancer has significantly improved. However, the growing population of these cancer survivors has led to the realization of multiple longterm complications secondary to their treatment. One of the most devastating long-term complications is the development of a second malignancy. CASE REPORTS: We report here the case of a 34-year-old man who developed stage IIB node-positive breast cancer almost 15 years following total body irradiation and allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia. To our knowledge, this is only the second report of a male breast cancer following allogeneic bone marrow transplantation (BMT). CONCLUSION: Survivors of primary cancer need lifelong monitoring for complications from their initial therapy.

The role of sentinel lymph node biopsy for melanoma.

Regional lymph nodes are a common site of melanoma metastases, and the presence or absence of melanoma in regional lymph nodes is the single most important prognostic factor for predicting survival. Furthermore, identification of metastatic melanoma in lymph nodes and excision of these nodes may enhance survival in a subgroup of patients whose melanoma has metastasized only to their regional lymph nodes and not to distant sites. Sentinel lymph node (SLN) biopsy was developed as a low morbidity technique to stage the lymphatic basin without the potential morbidity of lymphedema and nerve injury. The presence or absence of metastatic melanoma in the SLN accurately predicts the presence or absence of metastatic melanoma in that lymph node basin. When performed by experienced centers, the false-negative rate of SLN biopsy is very low. As such, the nodal basin that contains a negative SLN will usually be free of microscopic disease. Since occult micrometastatic disease affects only 12% to 15% of patients with melanoma, selective SLN dissection allows up to 85% of patients with melanoma to be spared a formal lymph node dissection, thus avoiding the complications usually associated with that procedure. While standard pathologic evaluation of lymph nodes may miss metastatic melanoma cells, more sensitive techniques are developing which may identify micrometastases more accurately. The clinical significance of these micrometastases remains unknown and is the subject of active investigations.

Is the Oncotype DX assay necessary in strongly estrogen receptor-positive breast cancers?

The 21-gene Oncotype DX recurrence score (RS) assay quantifies risk of distant recurrence and predicts benefit from chemotherapy in tamoxifen-treated estrogen receptor (ER)-positive, node-negative breast cancer. Although clinically useful, the assay costs roughly $4650. Because the assay is weighted heavily towards expression of ER, our objective was to determine its clinical utility in strongly ER-positive tumors. This was a retrospective study of Huntington Hospital patients undergoing an Oncotype DX assay between 2007 and 2010. Data collected included patient age, expression of ER, progesterone receptor (PR), HER2/neu, ki67, and p53, tumor size, node status, lymphovascular invasion, and nuclear grade. Of 133 total patients, 84 (63.2%) had strongly ER-positive tumors (≥90% expression). Only seven of 84 patients (8.3%) had a high risk RS (>30), indicating statistically significant predicted benefit from chemotherapy. All seven had intermediate to high ki67 expression (>20%) and lower PR expression (≤50%). Our study demonstrates that the clinical utility of the Oncotype DX assay in these patients is limited as most patients with strongly ER-positive tumors will have a low or intermediate RS. Future studies are needed to identify additional predictive factors in these patients with otherwise good prognosis.

Clinicopathologic factors associated with involved margins after breast-conserving surgery for invasive lobular carcinoma.

INTRODUCTION: Obtaining negative margins for patients undergoing breast-conserving surgery (BCS) for invasive lobular carcinoma (ILC) can be difficult because of the unique histologic pattern of ILC. Our goal was to determine whether any specific patient- or disease-related factors influenced margin status. PATIENTS AND METHODS: We retrospectively reviewed 211 patients with ILC treated from 1994 through 2004 to determine if specific clinical and pathologic factors influenced the ability to obtain negative margins. RESULTS: We identified 110 patients (52%) who underwent total mastectomy and 101 (48%) who underwent BCS. Among patients who underwent BCS, 50 (50%) had close or positive margins. Patients with close or positive margins were more likely to have architectural distortion on ultrasonography (vs. mass or calcifications; P = .049), to have undergone excisional biopsy (vs. core or fine-needle aspiration; P = .008), and to have associated ductal carcinoma in situ (P = .021). On multivariate analysis, only biopsy method retained significance (P = .006). CONCLUSION: Core needle biopsy is the preferred method of diagnostic biopsy before surgical intervention. With appropriate patient selection, most patients with early-stage ILC can undergo successful BCS.

Histologic changes associated with false-negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node-positive breast cancer before treatment.

BACKGROUND: A wide range of false-negative rates has been reported for sentinel lymph node (SLN) biopsy after preoperative chemotherapy. The purpose of this study was to determine whether histologic findings in negative SLNs after preoperative chemotherapy are helpful in assessing the accuracy of SLN biopsy in patients with confirmed lymph node-positive disease before treatment. METHODS: Eighty-six patients with confirmed lymph node-positive disease at presentation underwent successful SLN biopsy and axillary dissection after preoperative chemotherapy at a single institution between 1994 and 2007. Available hematoxylin and eosin-stained sections from patients with negative SLNs were reviewed, and associations between histologic findings in the negative SLNs and SLN status (true negative vs false negative) were evaluated. RESULTS: Forty-seven (55%) patients had at least 1 positive SLN, and 39 (45%) patients had negative SLNs. The false-negative rate was 22%, and the negative predictive value was 67%. The negative SLNs from 17 of 34 patients with available slides had focal areas of fibrosis, some with associated foamy parenchymal histiocytes, fat necrosis, or calcification. These histologic findings occurred in 15 (65%) of 23 patients with true-negative SLNs and in only 2 (18%) of 11 patients with false-negative SLNs (P = .03, Fisher exact test, 2-tailed). The lack of these histologic changes had a sensitivity and specificity for identifying a false-negative SLN of 82% and 65%, respectively. CONCLUSIONS: Absence of treatment effect in SLNs after chemotherapy in patients with lymph node-positive disease at initial presentation has good sensitivity but low specificity for identifying a false-negative SLN.

Feasibility and accuracy of sentinel lymph node biopsy after preoperative chemotherapy in breast cancer patients with documented axillary metastases.

BACKGROUND: The feasibility and accuracy of sentinel lymph node (SLN) biopsy in patients with breast cancer after preoperative chemotherapy has been demonstrated in a number of large, single-institution studies. However, a relative contraindication to SLN biopsy after preoperative chemotherapy is the presence of axillary metastases at initial diagnosis. The objective of this study was to determine the feasibility and accuracy of SLN biopsy after preoperative chemotherapy in patients with documented axillary metastases at presentation. METHODS: Between 1994 and 2002, 69 patients who had axillary metastases identified by ultrasound-guided, fine-needle aspiration underwent SLN biopsy after treatment on prospective, preoperative chemotherapy protocols. All but 8 patients underwent axillary lymph node dissection (ALND). Those 8 patients either declined additional surgery or were offered enrollment in other institutional protocols. RESULTS: The median patient age was 49 years, and the median primary tumor size was 4 cm. The SLN identification rate was 92.8%. Thirty-one of 64 patients (48.4%) had successfully mapped, positive SLNs. Sixty-one patients underwent ALND, including 5 patients who did not have an SLN identified. In the 56 patients in whom a SLN was identified and an ALND was performed, 10 patients had a false-negative SLN (25%). CONCLUSIONS: SLN biopsy was feasible after preoperative chemotherapy, even in patients who initially presented with cytologically proven, lymph node-positive disease. However, the false-negative rate of SLN biopsy in this group of patients was much higher than that observed in clinically lymph node-negative patients. Based on the current results, the status of the SLN cannot be used as a reliable indicator of the presence or absence of residual disease in the axilla in this patient population.

Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence.

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.

Intramammary lymph node metastases are an independent predictor of poor outcome in patients with breast carcinoma.

BACKGROUND: Breast carcinoma with intramammary lymph node (intraMLN) metastases is considered to be Stage II disease, even in the absence of axillary lymph node involvement. Nonetheless, little is known regarding the clinical significance of intraMLN metastases. The goals of the current retrospective analysis were to elucidate the clinical relevance of intraMLN metastases and to assess the relation between such metastases and outcome in patients with breast carcinoma. METHODS: One hundred ninety-six intraMLN specimens obtained between 1983 and 2003 were identified in the pathology database at The University of Texas M. D. Anderson Cancer Center (Houston, TX); 130 of these specimens were obtained in association with a primary breast malignancy. Data on the clinical and pathologic features of these specimens were collected and evaluated on univariate and multivariate analysis for potential correlations with 5-year rates of disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). The median follow-up duration was 36 months (range, 12-180 months). RESULTS: The median age of the 130 patients in the current study was 53 years (range, 27-84 years). Twenty-four patients (18%) had intraMLNs that were identified preoperatively by either mammographic or sonographic methods; in the remaining 106 cases, intraMLNs were detected on pathologic examination of surgical breast specimens. IntraMLN metastases were found in 28% of all cases (n = 36). Most patients who had intraMLN metastases (81%) also had axillary metastases; however, isolated intraMLN metastases were documented in 6 patients (5%). Univariate analysis revealed that patients with intraMLN metastases (compared with all other patients) had poorer 5-year rates of DFS (54% vs. 89%; P = 0.001), DSS (66% vs. 90%; P = 0.001), and OS (64% vs. 88%; P = 0.004). Furthermore, multivariate analysis indicated that intraMLN involvement was an independent predictor of reduced DFS (hazard ratio, 2.33; P = 0.03), DSS (hazard ratio, 5.32; P = 0.002), and OS (hazard ratio, 3.22; P = 0.006). CONCLUSIONS: The current retrospective analysis demonstrated that the presence of intraMLN metastases is an independent predictor of poor outcome in patients with breast carcinoma. Identification of an intraMLN on preoperative imaging should prompt further histopathologic assessment. Identification of malignant intraMLNs by lymphatic mapping may help to identify high-risk patients for whom further evaluation of the axillary lymph nodes is warranted despite otherwise clinically negative findings in the axilla.

Effective local control and long-term survival in patients with T4 locally advanced breast cancer treated with breast conservation therapy.

BACKGROUND: The presence of skin involvement has been accepted as a relative contraindication to breast preservation because it is believed to be associated with an increased local failure rate. This study was conducted to assess the outcome of a carefully selected group of patients who presented with breast cancer involving the skin and who had breast conservation therapy (BCT) following neoadjuvant chemotherapy. METHODS: Between 1987 and 1999, 33 patients with stage IIIB or IIIC breast cancer completed treatment consisting of four cycles of neoadjuvant chemotherapy, lumpectomy, radiation therapy, and consolidative chemotherapy. Clinicopathologic factors were analyzed and patients were followed for locoregional and distant recurrence. RESULTS: Initial median tumor size was 7 cm. All patients had skin involvement, defined as erythema, skin edema, direct skin invasion, ulceration, or peau d'orange. Following chemotherapy, median pathologic tumor size was 2 cm. Complete resolution of skin changes occurred in 29 patients (88%). At median follow-up time of 91 months in surviving patients, 26 patients (79%) were alive without evidence of disease. The 5-year, disease-free survival rate was 70%, and the 5-year overall survival rate was 78%. The actuarial ipsilateral breast cancer recurrence rate was 6% at 5 years. CONCLUSIONS: Patients who present with T4 breast cancer who experience tumor shrinkage and resolution of skin changes with neoadjuvant chemotherapy represent a select group of patients who can have BCT. These patients have favorable rates of long-term local control and survival. Mastectomy is not mandatory for all patients with breast cancer who present with skin involvement.