Zhi Min Shao

Chemokine decoy receptor d6 plays a negative role in human breast cancer.

Chemokine binding protein D6 is a promiscuous decoy receptor that can inhibit inflammation in vivo; however, the role it plays in cancer is not well known yet. In this study, we showed for the first time that human breast cancer differentially expressed D6 and the expression could be regulated by some cytokines. More importantly, overexpression of D6 in human breast cancer cells inhibits proliferation and invasion in vitro and tumorigenesis and lung metastasis in vivo. This inhibition is associated with decreased chemokines (e.g., CCL2 and CCL5), vessel density, and tumor-associated macrophage infiltration. Furthermore, D6 expression is inversely correlated to lymph node metastasis as well as clinical stages, but positively correlated to disease-free survival rate in cancer patients. Therefore, D6 plays a negative role in the growth and metastasis of breast cancer. (Mol Cancer Res 2008;6(8):1276–88)

Development and trends of surgical modalities for breast cancer in China: a review of 16-year data.

BackgroundSurgery is the most important treatment for nonmetastatic breast cancer; however, the utilization of modern surgical techniques in management of breast cancer in mainland China has not been reported.MethodsThe medical records of 5887 consecutive breast cancer patients treated surgically in the past 16 years were reviewed retrospectively; the utilization of different surgical modalities and associated clinical outcomes were analyzed.ResultsMedian age of all patients was 50 (range 16–92). About 1015 patients were staged as 0–I, 3569 stage II, 517 stage III, and 786 cases could not be staged. Extensive radical mastectomy (ERM), radical mastectomy (RM), modified radical mastectomy (MRM), simple mastectomy (SM), and breast-conserving surgery (BCS) were used in 8%, 27.2%, 55.7%, 1.5%, and 6.3% of patients, respectively. In addition, 1.3% of patients received breast reconstruction. The proportion of early-stage breast cancer increased, and the surgery patterns varied. MRM gradually replaced ERM and RM. The prevalence of BCS began to increase from the mid-1990s and currently represents about 12%. The prevalence of reconstruction also increased and now accounts for 5%. Age, pathologic pattern, and TNM staging affected the choice of surgery modalities markedly. Although patients receiving RM/ERM had worse survival than those receiving BCS/MRM, the survival outcomes of these four groups were similar in the early-stage population.ConclusionsMRM remains the most-used surgical modality in operable breast cancer, although the utilization of BCS for early-stage disease has increased rapidly in last decade. Reconstruction following mastectomy as an alternative to BCS is available. Breast-conserving therapy (BCT) and MRM provide similar local controls and long-term survival for breast cancer. Selection of appropriate candidates for a certain surgery requires an assessment of the patient’s age and clinical and pathological characteristics of the tumor.

Molecular subtype approximated by quantitative estrogen receptor, progesterone receptor and Her2 can predict the prognosis of breast cancer

AIMS AND BACKGROUND To investigate the clinicopathological characteristics and prognosis of breast cancer subtypes classified by quantitative estrogen receptor (ER), progesterone receptor (PR), and Her2. METHODS AND STUDY DESIGN 923 patients with primary breast cancer having a median age of 53 years who were treated at the Cancer Hospital of Fudan University in Shanghai between January 2002 and June 2004 were retrospectively analyzed. Four molecular subtypes were constructed from the immunohistochemical results of quantitative hormone receptor (HR) and Her2 status. HR+ was defined as ER+ and PR+, HR+/- as ER/PR+ at lower levels or lacking either ER or PR, and HR- as both ER- and PR-. The four subtypes were HR+/Her2-, HR+/-/Her2-, HR-/Her2- (triple-negative), and Her2+. Clinical and pathological parameters, disease-free survival (DFS), and overall survival (OS) measurements were compared between patients with different molecular subtypes. RESULTS The proportions of HR+/Her2-, HR+/-/Her2-, triple-negative, and Her2+ breast cancer were 36.6% (338/923), 22.9% (211/923), 20.6% (190/923), and 19.9% (194/923). The median follow-up was 49.0 months (4-77 months). In 145 cases disease recurrence or death occurred. In multivariate analysis with the HR+/Her2- subtype taken as the reference category, triple-negative and Her2+ subtypes were associated with increased recurrence and death with a hazard ratio (HR) of 2.05 (95% CI 1.31-3.20; P = 0.002) and 1.89 (95% CI 1.20-2.97, P = 0.006) for DFS and 2.84 (95% CI 1.45-5.55; P = 0.002) and 2.95 (95% CI 1.51-5.77, P = 0.002) for OS, respectively; the HR+/-/Her2- subtype was marginally associated with poor prognosis with HR 1.51 (95% CI 0.94-2.43; P = 0.088) and 1.90 (95% CI 0.92-3.94; P = 0.084) for DFS and OS, respectively. CONCLUSIONS Breast cancer subtypes based on quantitative ER, PR, and Her2 may be predictive of prognosis. Patients whose tumors were not HR+/Her2- had a worse outcome in our study.

The role of mammographic calcification in the neoadjuvant therapy of breast cancer imaging evaluation.

Introduction Investigate the patterns of mammographically detected calcifications before and after neoadjuvant chemotherapy (NACT) to determine their value for efficacy evaluation and surgical decision making. Methods 187 patients with malignant mammographic calcifications were followed to record the appearances and changes in the calcifications and to analyze their responses to NACT. Results Patients with calcifications had higher rates of hormonal receptor (HR) positive tumors (74.3% versus 64.6%) and HER2 positive tumors (51.3% versus 33.4%, p = 0.004) and a similar pathologic complete response (pCR) rate compared to patients without calcifications (35.4% versus 29.8%). After NACT, the range of calcification decreased in 40% of patients, increased in 7.5% and remained stable in 52.5%; the calcification density decreased in 15% of patients, increased in 7.5% and remained stable in 77.5%; none of these change patterns were related to tumor response rate. No significant correlation was observed between the calcification appearance (morphology, distribution, range, diameter or density) and tumor subtypes or pCR rates. Among patients with malignant calcifications, 54 showed calcifications alone, 40 occurred with an architectural distortion (AD) and 93 with a mass. Calcifications were observed inside the tumor in 44% of patients and outside in 56%, with similar pCR rates and patterns of change. Conclusions Calcification appearance did not clearly change after NACT, and calcification patterns were not related to pCR rate, suggesting that mammogram may not accurate to evaluate tumor response changes. Microcalcifications visible after NACT is essential for determining the extent of excision, patients with calcifications that occurred outside of the mass still had the opportunity for breast conservation.

Patients with Nipple-Areola Paget’s Disease and Underlying Invasive Breast Carcinoma Have Very Poor Survival: A Matched Cohort Study

Paget’s disease (PD) of the breast is a rare disease. The survival rate of PD was reported to depend on the characteristics of the underlying carcinoma. This study aimed to investigate the characteristics and survival rate of PD patients with underlying invasive breast carcinoma (IBC). Fifty-two patients were diagnosed with PD and an associated IBC from 2001 to 2005 in Fudan University Shanghai Cancer Center. Twenty-four (46.2%) had no clinical manifestation of PD and were diagnosed unexpectedly by a histologic examination. The 52 patients were all recruited in this study as the PD group. They tended to have greater chances of lymph node involvement (53.8% vs. 35.7%), lower hormone receptor expression (34.6% vs. 69.7%), higher human epidermal growth factor receptor 2 (HER2) expression (76.9% vs. 21.3%), and worse survival (5-year relapse-free survival (RFS) 52.2% vs. 86.7%, P<0.01; breast cancer-specific overall survival (OS) 62.1% vs. 91.8%, P<0.01) when compared with patients diagnosed with IBC. A matched study was then performed to investigate whether the poor survival of patients in the PD group was due to the unfavorable prognosis of the underlying IBC. One hundred and fifty-six (3∶1 ratio of controls to PD patients) patients diagnosed with IBC only were recruited into the matched group. The match was conducted according to four variables: dimension of IBC, lymph node status, hormone receptor status and HER2 status. The 5-year RFS (52.2% vs. 81.4%, P<0.01) and OS (62.1% vs. 85.9%, P<0.01) were both lower for patients in the PD group than those in the matched group. Patients with PD and underlying IBC had poor survival. Their survival was worse than that of patients with IBC of similar stage and characteristics. For patients with no clinical PD manifestation who were histologically diagnosed as PD, survival might be worse compared to patients with clinically diagnosed PD.

Breast cancer in Chinese elderly women: Pathological and clinical characteristics and factors influencing treatment patterns

The aims of this study are to describe tumor characteristics and treatment patterns of elder breast cancer patients and to determine the factors influencing local and systemic treatments. This retrospective cohort included 866 patients (>or=60 years) referred for surgery between January 2002 and December 2006. The patients were divided into four groups according to age. Elderly women had larger tumors at diagnosis with more mucinous carcinomas, more estrogen/progesterone-positive, lower Ki-67 labeling indices and less c-erbB2 positive tumors. Comorbidities were more often recorded for older patients. They were more likely to undergo simple mastectomy or breast-conserving surgery, less likely to receive adjuvant chemotherapy and radiotherapy, compared with their younger counterparts. Multinomial and binary logistic regression showed that age was independently associated with local and systemic treatments. Our data suggest that the tumors of elderly patients are biologically more favorable, and elderly women appear to receive less aggressive treatments.

Overweight as a prognostic factor for triple-negative breast cancers in Chinese women

Purpose Obesity is associated with poorer outcomes in patients with hormone receptor-positive breast cancers, but this association is not well established for women with triple-negative breast cancers (TNBC). Here, we investigated the prognostic effects of body mass index (BMI) on clinical outcomes in patients with TNBC. Methods We identified 1106 patients with TNBC who met the inclusion criteria and were treated between January 2002 and June 2012. Clinical and biological features were collected to evaluate the relation between BMI and breast cancer-specific survival (BCSS) and overall survival (OS) after controlling for other clinically significant variables. Results Of 1106 patients, 656 (59.3%) were normal weight (BMI ≤24) and 450 patients (40.7%) were overweight(BMI>24). Median follow-up time was 44.8 months. Breast cancer specific death was observed in 140 patients. After adjusting for clinicopathologic risk factors, overweight was associated with OS (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.04-2.06, P =0.028) but not BCSS (HR: 1.34, 95% CI: 0.90–2.01, P =0.15)in all the patients with TNBC. When stratified with menopausal status, overweight was associated with BCSS and OS (HR: 2.27, 95% CI: 1.11-4.63, P = 0.024 and HR: 2.16, 95% CI: 1.21-3.87, P = 0.010, respectively) in premenopausal women. BMI was not associated with BCSS or OS in postmenopausal women. Conclusions Overweight is an independent prognostic factor of OS in all women with TNBC, and menopause status may be a mitigating factor. Among premenopausal women, overweight women are at a greater risk of poor prognosis than normal weight women. If validated, these findings should be considered in developing preventive programs.

Fiberoptic ductoscopy-guided intraductal biopsy improve the diagnosis of nipple discharge.

Abstract:  Fiberoptic ductoscopy (FDS)‐guided intraductal biopsy is a minimally invasive technique developed to obtain pathologic diagnoses for patients with spontaneous nipple discharge. We performed biopsies of 53 intraductal lesions from March 2006 to April 2007 followed by surgical microdochectomy. FDS‐guided intraductal biopsy was shown to be a minimally invasive, safe, and convenient technique with a high ability (90.6%) to get adequate samples. Twenty‐seven solitary papillomas, 12 multiple intraductal papilloma, five ductal hyperplasia, three ductal carcinoma in situ, and one invasive ductal carcinoma were diagnosed. Compared with conventional microdochectomy, FDS‐guided intraductal biopsy can significantly increase the detection rate of solitary papilloma (40.7% versus 92.6%, p < 0.05). It should be a routine procedure after intraductal lesion found by screening FDS. Since it would underestimate all multiple intraductal papilloma and some (50%) cancer, microdochectomy is inevitable if biopsies show atypical ductal hyperplasia.

Malignant calcification is an important unfavorable prognostic factor in primary invasive breast cancer.

To explore the clinical characteristics and prognostic value of malignant calcification in operable breast cancer.

Retrospective analysis of 119 Chinese noninflammatory locally advanced breast cancer cases treated with intravenous combination of vinorelbine and epirubicin as a neoadjuvant chemotherapy: a median follow-up of 63.4 months

BackgroundThis study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC).MethodsOne-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67).ResultsPatients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p = 0.034, p = 0.027, respectively). A significantly increased risk of death was associated with lack of pre-ER expression (p = 0.002). Among patients with non-pCR, those with a pathological response at the tumor site with special involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk of disease relapse and death (p < 0.001, p = 0.001, respectively).ConclusionThis study suggests the promising use of a VE regimen as NC for Chinese NLABC after a median follow-up of 63.4 months. Pathological response in the tumor site, pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important variables that predicted long-term outcome. Patients with pathological special involvement at the primary site after NC had the lowest survival rates.