Predicting Non-sentinel Lymph Node Metastasis in a Chinese Breast Cancer Population with 1-2 Positive Sentinel Nodes: Development and Assessment of a New Predictive Nomogram.

BACKGROUND: We have developed a new nomogram to predict the probability of a patient with 1-2 metastatic sentinel lymph nodes (SLNs) to present further axillary disease. METHODS: Data were collected from 480 patients who were diagnosed with 1-2 positive lymph nodes and thus underwent axillary lymph node dissection between March 2005 and June 2011. Clinical and pathological features of the patients were assessed with multivariable logistic regression. The Shanghai Cancer Center Non-SLN nomogram (SCC-NSLN) was created from the logistic regression model. This new model was subsequently applied to 481 patients from July 2011 to December 2013. The predictive accuracy of the SCC-NSLN nomogram was measured by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: Based on the results of the univariate analysis, the variables that were significantly associated with the incidence of non-SLN metastasis in an SLN-positive patient included lymphovascular invasion, neural invasion, the number of positive SLNs, the number of negative SLNs, and the size of SLN metastasis (P < 0.05). Using multivariate analysis, lymphovascular invasion, the number of positive SLNs, the number of negative SLNs, and the size of SLN metastasis were identified as independent predictors of non-SLN metastasis. The SCC-NSLN nomogram was then developed using these four variables. The new model was accurate and discriminating on both the modeling and validation groups (AUC: 0.7788 vs 0.7953). The false-negative rates of the SCC-NSLN nomogram were 3.54 and 9.29 % for the predicted probability cut-off points of 10 and 15 % when applied to patients who have 1-2 positive SLNs. CONCLUSION: The SCC-NSLN nomogram could serve as an acceptable clinical tool in clinical discussions with patients. The omission of ALND might be possible if the probability of non-SLN involvement is <10 and <15 % in accordance with the acceptable risk determined by medical staff and patients.

Predicting sentinel lymph node metastasis in a Chinese breast cancer population: assessment of an existing nomogram and a new predictive nomogram.

We assessed the MSKCC nomogram performance in predicting SLN metastases in a Chinese breast cancer population. A new model (the SCH nomogram) was developed with clinically relevant variables and possible advantages. Data were collected from 1,545 patients who had a successful SLN biopsy between March 2005 and November 2011. We validated the MSKCC nomogram in the modeling and validation group. Clinical and pathologic features of SLN biopsy in modeling group of 1,000 patients were assessed with multivariable logistic regression to predict the presence of SLN metastasis in breast cancer. The SCH nomogram was created from the logistic regression model and subsequently applied to 545 consecutive SLN biopsies. By multivariate analysis, age, tumor size, tumor location, tumor type, and lymphovascular invasion were identified as independent predictors of SLN metastasis. The SCH nomogram was then developed using the five variables. The new model was accurate and discriminating (with an AUC of 0.7649 in the modeling group) compared to the MSKCC nomogram (with an AUC of 0.7105 in the modeling group). The area under the ROC curve for the SCH nomogram in the validation population is 0.7587. The actual probability trends for the various deciles were comparable to the predicted probabilities. The false-negative rates of the SCH nomogram were 1.67, 3.54, and 8.20 % for the predicted probability cut-off points of 5, 10, and 15 %, respectively. Compared with the MSKCC nomogram, the SCH nomogram has a better AUC with fewer variables and has lower false-negative rates for the low-probability subgroups. The SCH nomogram could serve as a more acceptable clinical tool in preoperative discussions with patients, especially very-low-risk patients. When applied to these patients, the SCH nomogram could be used to safely avoid a SLN procedure. The nomogram should be validated in various patient populations to demonstrate its reproducibility.

Adjuvant therapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and 5-fluorouracil.

We performed a retrospective study of 856 breast cancer patients in our hospital, to compare the therapeutic effect of pirarubicin with cyclophosphamide and 5-fluorouracil (CPF) with the standard epirubicin-based regimen (CEF) in adjuvant treatment of breast cancer. Patients were given cyclophosphamide and 5-fluorouracil 500 mg/m(2) each, and either pirarubicin 40 mg/m(2) or epirubicin 75-100 mg/m(2) , every 3 weeks, six cycles. A total of 233 patients used CPF and 623 patients used CEF regimen. The clinical and pathologic characteristics were well balanced between the two groups. The median follow-up time was 41 months, relapse-free survival (RFS) and overall survival (OS) were similar in both groups, p = 0.561 and p = 0.783, respectively. No treatment-related congestive heart failure or death was observed in either group. Regardless of chemotherapy regimens, only tumor size, lymph node status, and ER status were predictive factors in multivariate survival analysis. In stratified analysis, the total hazard ratio estimate for RFS was 0.876 (95% CI 0.561-1.369; p = 0.562), not in favor of either regimen, and no significant difference was observed in any subgroups between the two treatment arms. Our study verified that 3 weekly CPF gives the same efficacy and safety as the standard CEF; both CPF and CEF are the effective regimens that can be used in adjuvant chemotherapy of breast cancer.

[Screening of microsatellite markers associated with cold tolerance of large yellow croaker (Pseudosciaena crocea R.)].

Cold tolerance is one of the major economic characters in fish. In order to discuss the cold tolerance of large yellow croaker (Pseudosciaena crocea R.), fifteen fluorescent dye-labeled microsatellite markers were applied to detect genetic differences between F1 offsprings of cold tolerance group and normal group of large yellow croaker by SSR-PCR. Each group contained 20 randomly and separately sampled individuals. As a result, marker LYC0002 five alleles (LYC0002(104 bp), LYC0002(106 bp), LYC0002(108 bp), LYC0002(110 bp), and LYC0002(112 bp)) were amplified with marker LYC0002 in both groups and 60% (12/20) of individuals had allele LYC0002(112 bp) in cold tolerance group exclusively, which indicated that this allele is probably sensitive to temperature and associated with gene for cold tolerance. In addition, four alleles (LYC0002(106 bp), LYC0002(108 bp), LYC0002(110 bp), and LYC0002(112 bp)) were sequenced individually. Sequence alignments showed that LYC0002(112 bp) allele contains 10 (CA) repeats, the remaining three alleles lacked one (CA) one by one, corresponding to the stepwise mutation model (SMM) of microsatellite.

Clinicopathological features of breast cancer patients with nipple discharge.

The demographic features and prognostic profiles of breast cancer patients with nipple discharge (ND) have not been well elucidated in previous studies. We therefore performed a retrospective study of female unilateral breast cancer patients that underwent surgery. According to the initial symptoms at diagnosis, a total of 3,317 patients were categorized into the ND (2.74%) and non-ND (NND; 97.26%) subgroups. Survival curves were performed with the Kaplan-Meier method and annual recurrence hazard was estimated by the hazard function. The proportion of larger tumors was lower in patients with ND than in the NND subgroup (P=0.019). In addition, 22.22% of patients with ND had positive lymph nodes in the axilla as compared to 51.06% of those without ND (P<0.001). Multivariate logistic regression analysis showed that axillary lymph node (ALN) status (P=0.003) and Cathepsin-D status (P=0.025) were independent prognostic factors for ND. In the univariate survival analysis, a significant difference in recurrence-free survival (RFS) was found between patients with and without ND (P=0.014). As ND and ERBB2 status were time-varying covariates (global test, both P<0.05), the Cox non-proportional hazards regression model was used. In this model, ND status (P=0.028; RR=2.174, 95% CI 1.086­4.351), as well as tumor size (P<0.001; RR=1.779, 95% CI 1.406-2.250), ALN status (P<0.001; RR=2.257, 95% CI 1.886-2.702), ERBB2 status (P=0.011; RR=0.759, 95% CI 0.613-0.940) and use of adjuvant chemotherapy (P=0.048; RR=0.642, 95% CI 0.414-0.995) were independent prognosticators for RFS. Regarding hazard peaks, patients without ND showed an early major recurrence surge peaking at 1.5 years after surgery, while the corresponding peak for the ND subgroup was at 3.5 years. Furthermore, the risk of early recurrence for women with ND was lower than that for the NND subgroup. Our findings suggest that biological behavior and prognostic profiles differ significantly between patients with and without ND. This suggests that further studies are required to elucidate these two distinctive disease entities.

Clinicopathological features of the triple-negative tumors in Chinese breast cancer patients.

In order to analyze the clinicopathological features of Chinese triple negative tumors, we performed a retrospective study of 1993 female unilateral breast cancer patients undergoing surgery in Cancer Hospital of Fudan University, Shanghai, China. Survival curves were performed with Kaplan-Meier method and annual recurrence hazard was estimated by hazard function. We observed that the rate of larger tumors in triple negative patients was higher than that in HR+/ERBB2- women, but lower than that in ERBB2+ subgroup (P = 0.0001). In addition, 21.83% of triple negative patients had four or more axillary lymph nodes involved as compared to 27.40% of ERBB2+ women and 22.75% of HR+/ERBB2- subgroup (P = 0.0056). In the survival analysis, we found a statistical significance for recurrence-free survival (RFS) among the three subgroups (P = 0.0037), with the rate of 72.89% for ERBB2+ patients, 78.40% for HR+/ERBB2- ones and 75.76% for triple negative ones at the 11th year respectively. When it came to hazard peaks, discrepancies existed in different subgroups. Similar to HR+/ERBB2- patients, triple negative subgroup showed an early major recurrence surge peaking at approximately year 2.5 as opposed to ERBB2+ counterparts with a tapering sharp at the 1st year. Furthermore, the first peak of triple negative tumors was higher than that of HR+/ERBB2- patients, but lower than that of ERBB2+ ones. Therefore, our findings suggested biological characteristics and prognostic outlook of Chinese triple negative breast cancers might be more favorable and somewhat different from those in Western populations.

[BRCA1/2 gene mutation in Chinese familial breast cancer patients: a multi-center report of 115 cases].

OBJECTIVE: To study the BRCA1/2 gene mutation frequency and characteristics in Chinese familial breast cancer patients. METHODS: Denaturing high-performance liquid chromatography (DHPLC) and following DNA sequencing in BRCA1/2 gene whole coding region and exon-intron splicing sites were performed in the specimens obtained during operation from 115 probands of familial breast cancer from 4 breast cancer centers in China. RESULTS: Fourteen cases of gene mutation (11 in BRCA1 and 3 in BRCA2) were found in the 115 breast cancer specimens with an overall mutation rate of 12.2%. After stratification with number of breast cancer patients in family, the frequency of mutation did not change significantly. The average age of disease onset of the families carrying BRCA1/2 mutations was significantly younger than that of the families without mutations (P < 0.01), and the higher the number of young patients in family, the higher the mutation rate. CONCLUSION: In Chinese familial breast cancer patients, age of disease-onset is an effective predictive factor of BRCA1/2 mutation, however, the predictive effect of the number of affective relatives in family is not good.

[A retrospective study of 129 cases with immediate breast reconstruction after skin-sparing mastectomy for breast cancer].

OBJECTIVE: To evaluate the oncologic safety, indications and aesthetic results for skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR). METHOD: One hundred and twenty-nine breast cancer patients treated by SSM + IBR from October 1999 to May 2007 were reviewed. Reconstructive techniques included latissimus dorsi flaps (38 patients), implants only (2 patients), latissimus dorsi flaps plus implants (61 patients), pedicled transverse rectus abdominis myocutaneous (TRAM) flaps (25 patients) and deep inferior epigastric artery perforator (DIEP) flaps (3 patients). Aesthetic results were judged by patients' self-evaluation. RESULTS: Mean duration of hospitalization was 18.6 days. Time of first chemotherapy was 5.2 days after operation. Eleven patients (11/63, 17.5%) developed capsular contracture and 24 patients (24/99, 24.2%) developed seroma in the donor site. Nine patients (9/28, 32.1%) developed partial fat necrosis in TRAM and DIEP flaps. The satisfaction with the aesthetic results of the reconstructive breast was significantly lower in irradiated patients than non-irradiated ones. Median follow-up time was 11 months. Five patients developed local recurrence and 7 patients with metastasis. CONCLUSIONS: SSM with IBR can be used for the 0 to II a stage breast cancer patients, with surgical oncologic and aesthetic satisfaction. Radiotherapy has an adverse effect on the reconstructive breast. Delayed or delayed-immediate reconstructions are recommended for patients indicated to postoperative radiotherapy.

[Application of methylene blue dye to sentinel lymph node biopsy in breast cancer and its influencing factors].

BACKGROUND & OBJECTIVE: Tracer is one of the important influencing factors for the successiveness of sentinel lymph node biopsy (SLNB) for breast cancer. This study was to evaluate the efficacy of methylene blue dye (MBD) as a tracer in SLNB for breast cancer, and to analyze its influencing factors. METHODS: From Mar. 2005 to Feb. 2006, 101 operable breast cancer patients with clinically negative axillary lymph node were enrolled. MBD was used alone as the tracer agent for SLNB. Axillary dissection was performed after SLNB. All sentinel lymph nodes (SLNs) were examined pathologically with HE staining. RESULTS: In this series, the identification rate of SLNs was 96.04% (97/101). The false negative rate was 11.76% (4/34). Excluding the patients received neoadjuvant chemotherapy, the false negative rate was 7.41% (2/27). The mean number of SLNs harvested was 2.05 in each patient. The size of SLNs was related to the pathologic results. Histological type, neoadjuvant chemotherapy, excisional biopsy had no impact on the identification rate of SLNs. The number of SLNs was correlated to the false negative rate of SLNB. The body mass index (BMI) was related to the identification rate of SLNs and the false negative rate of SLNB. No allergic reaction and skin necrosis had been observed. CONCLUSIONS: MBD is a safety, reliable tracing agent for SLNB in breast cancer. Improved tracing technology is needed for the patients with higher BMI.

[5589del8: the recurrent mutation of BRCA1 gene in Chinese breast cancer patients].

OBJECTIVE: To study the "hot spot" of BRCA1/2 gene mutations in Chinese mainland breast cancer population. METHODS: The known BRCA1/2 gene mutations in author's previous studies were reanalyzed by denaturing high performance liquid chromatography and DNA sequencing method in 177 patients with early onset breast cancer or affected relatives and 426 sporadic breast cancer patients from four breast cancer centers in China. RESULTS: Three cases were found with BRCA1 5589del8 mutation out of 247 hereditary-predisposing breast cancer patients (70 patients in previous study and 177 patients in current study) and 2 cases with BRCA1 5589del8 mutation out of 426 sporadic breast cancer patients. They had similar even same haplotype. CONCLUSION: BRCA1 5589del8 mutation is likely to be the "founder mutation" in Chinese population, but it should be confirmed by further studies.

[Evaluation of intraoperative touch imprint cytology of sentinel lymph node for breast cancer].

OBJECTIVE: To evaluate the intraoperative touch imprint cytology as an diagnostic method of sentinel lymph node for breast cancer patient. METHODS: Sentinel lymph node biopsy was performed in 105 selected early breast cancer patients, and sentinel lymph node was identified in 101 (96.19%) of these patients. Axillary lymph node dissection was also performed in almost all the patients. All the sentinel lymph nodes were cut into 2-3 mm pieces along the long axis. Touch imprint was made of each piece of the sentinel lymph node, then air-dried, and finally stained with H&E. Intraoperative touch imprint cytology results were compared with the final paraffin H&E pathology. All sentinel nodes were cut into 4 microm sections every 100-microm interval, and the series sections were stained with H&E. RESULTS: 202 sentinel lymph nodes were identified in 101 breast cancer patients. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value of intraoperative imprint cytology for 202 sentinel nodes was 92.1%, 98.8%, 97.5%, 94.6% and 98.2%, respectively; which was 89.3%, 98.6%, 96.0%, 96.2% and 96.0%, respectively in the 101 patients with identified sentinel node. Compared with the series sections, the sensitivity, specificity, accuracy, positive predictive value, negative predictive value of intraoperative imprint cytology for sentinel nodes was 83.3%, 98.8%, 95.5%, 94.6% and 95.8%, respectively; and it was 81.3%, 100.0%, 94.1%, 100.0% and 92.0%, respectively in 101 patients with identified sentinel node. CONCLUSION: Touch imprint cytology is a simple, effective and rapid method for intraoperative pathological evaluation of sentinel lymph node for breast cancer patient, which has a high concordance with the paraffin results, and can provide accurate and rapid diagnosis information for the surgeon during operation.

[Clinico-pathological features of ER+/PR+ and ER+/PR- breast tumors: a comparative study of 5211 cases].

OBJECTIVE: To compare the differences in the clinicopathological and molecular biological features between the breast cancer patients with estrogen receptor (ER)+/progesterone receptor (PR)+ or ER+/PR- tumors. METHODS: The clinicopathological data of 3124 female breast cancer patients with known ER/PR expression status, 2220 being ER+/PR+ and 904 being ER+/PR-, and 1484 being ER-/PR-, were analyzed retrospectively. Immunohistochemistry was used to detect the expression of c-erb and cathepsin D in the tumor specimens. RESULTS: The average peak onset age was 50 years in both the ER+/PR+ and ER+PR- patients, and the mean age of the ER+/PR+ patients was 52.40 years, not significantly different from that of the ER-/PR- patients (52.57 years, P = 0.709). The peak onset age of the ER+ patients was 50 years, significantly higher that that of the ER- patients (48 years, P = 0.001), and the mean age of the ER+ patients was 52.46 years, significantly higher than that of the ER- patients (51.42 years, P = 0.001). Univariate analysis showed that ER+/PR- tumors tended to be larger. 24.8% of the ER+/PR- patients had 4 or more metastatic lymph nodes, a rate significantly higher than that of the ER+/PR- patients (20.7%, P = 0.004). The tumors of 18% of the ER+/PR- patients were at the grade III, a rate significantly higher than that of the ER+/PR+ patients (13.5%, P = 0.008). The strong positivity rate of the ER+/PR+ tumors was 23.4%, ignorantly higher than hat of the ER+/PR- tumors (11.2%, P = 0.000). The c-erB-2 positive rate of the ER+/PR+ tumors was 19.7%, significantly lower than that of the ER+/PR- tumor group (28.7%, P = 0.000). The cathepsin D positive rate of the ER+/PR- group was 76.9%, significantly higher than that of the ER+/PR- group (71.9%, P = 0.005). Multivariate analysis indicated that positive PR expression was associated with the level of ER (OR = 1.792, 95% CI = 1.484 - 2.164, P = 0.000), cathepsin D (OR = 1.380, 95% CI = 1.023 - 1.862, P = 0.035) and c-erbB-2 (OR = 0.639, 95% CI = 0.463 - 0.883, P = 0.007). CONCLUSION: ER+/PR+ and ER+/PR- tumors may have identical etiology. The mechanism of whether PR is expressed in ER+ breast cancer may be caused by different factors, which causing many different aspects. According to these differences, new target of therapy may provide the possibility of improving the response and prognosis for patients with ER+/PR- tumors.

[A study of the combination of vinorelbine and epirubicin as neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer].

OBJECTIVE: To evaluate the clinical efficacy and toxicity of vinorelbine (N) and epirubicin (E) as the neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer (LABC). METHODS: From September 2001 to December 2004, 158 patients with LABC were treated with NE chemotherapy before operation. Neoadjuvant chemotherapy containing vinorelbine (N), 25 mg/m(2) (days 1 and 8) and epirubicin (E), 60 mg/m(2) (days 1) was administered every 3 weeks for three cycles before local treatment. RESULTS: Response in the breast: the clinical objective response was 81.6% [23.4% (37/158) cCR and 58.2% (92/158) PR], 16.5% (26/158) SD and 1.9% (3/158) PD. Pathological complete response was found in 29 cases (18.3%). Eighteen cases (26.5%) who have positive FNA result in the axillary lymphnode before chemotherapy showed negative result in the surgery specimen. The most common toxicities were neutropenia, alopecia and nausea/vomiting. Neutropenia grade 3 - 4 was reported in 111 patients (70.3%) and there was no toxic deaths. CONCLUSIONS: The combination of vinorelbine and epirubicin is a very active and well-tolerated regimen as neoadjuvant chemotherapy for the LABC.

Breast conservative therapy in east part of China: a retrospective cohort study.

PURPOSE: To compare the effects of breast conservative therapy (BCT) with modified radical mastectomy (MRM) in women with early stage breast cancer in the east part of China. We conducted a matched retrospective cohort study using data on patients derived from a prospectively collected breast cancer database. METHODS: We used the database that included patients who received MRM or BCT from 1995 to 2002 in our hospital. The match was conducted according to four variables: age at diagnosis, axillary lymph node status, hormone receptor status, and the dimension of tumor. The match ratio was 1:2. MRM group were patients who received MRM treatment (n=254). BCT group were patients who received BCT treatment (n=127). Median follow-up time for the BCT group and MRM group were 58 and 49 months, respectively. The differences of incidence of loco-regional recurrence, disease free survival, and overall survival at 5 years were compared. RESULTS: There were no significant differences in incidence of loco-regional recurrence, DFS and OS at 5 years between the two groups of patients. The incidence of loco-regional recurrence was 1.84% in MRM group and 3.39% in BCT group (P=0.55). The DFS in MRM and BCT patients were 91.57 and 86.04% (P=0.37); the OS in MRM and BCT patient were 97.57 and 96.73% (P=0.66). CONCLUSIONS: For appropriate breast cancer patients, classic lumpectomy plus axillary dissection and postoperative radiotherapy lead to excellent local control and good survival rate in our study. The BCT can result in the same effects as MRM in Chinese breast cancer patients with better cosmetic appearances.

[Analysis of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives].

OBJECTIVE: To study the BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives. METHODS: Genomic DNA from 41 patients' peripheral blood mononuclear cells was studied by using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and DNA sequencing. BRCA1 mutations were detected in the whole gene sequence. RESULTS: Disease-related BRCA1 mutations were detected in 3 of the 41 patients studied. Two of the 3 patients were younger than 35 years old, and one patient with family history. CONCLUSION: The incidence of BRCA1 mutations in Chinese patients with early onset breast cancer is similar to that reported from western countries, but the incidence of mutations in Chinese breast cancer patients with affected relatives is comparatively low.

The analysis of BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives.

To study the BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives, 41 patients' genomic DNA from peripheral mononuclear blood cells was studied by using single strand conformational polymorphism (SSCP) and DNA sequencing. The BRCA1 mutations were detected in the whole gene sequence. Three novel disease-causing mutations (c.582C>T, c.735C>T and c.2790delT) occurred in all the patients. Two occurred in the patients younger than 35 years old (9.1%) and one in the patients with affected relatives (5%). Additional sequence variants identified included a novel missense mutation of unknown significance and six polymorphisms. The prevalence of BRCA1 mutations in Chinese patients in Shanghai with early onset breast cancer is similar to that observed in western women, but the incidence of mutations in breast cancer patients in Shanghai with affected relatives isn't as high as that in western women.

Significance of Apoptosis and Apoptotic-Related Proteins, Bcl-2, and Bax in Primary Breast Cancer.

Apoptosis and expression of apoptosis-regulating proteins, Bcl-2 and Bax, have been observed in human breast carcinomas. The authors investigated whether expression of Bcl-2 and Bax proteins and apoptotic index (AI) had significance in cases of primary breast cancer. The authors evaluated Bcl-2 and Bax immunoreactivity and AI in primary breast cancers with the ApopTag method in 91 breast cancer patients retrospectively with long-term follow-up (median 60 months). Bcl-2 expression was seen in 60 (65.9%) cases and Bax expression was observed in 59 (64.8%) cases. Increased Bcl-2 and absence or low Bax immunoreactivity were significantly associated with low AI, high tumor grade, axillary lymph node involvement, postoperative recurrence, and metastasis. Thirty-five (38.5%) samples expressed high AI, which correlated with low tumor grade, absent axillary lymph node metastasis, and low levels of Bcl-2 with Bax overexpression. In univariate analysis, the variables associated with short relapse-free survival (RFS) and overall survival (OS) were large tumor size, axillary lymph node involvement, high histologic grade, low AI, high Bcl-2 expression, and absence or low Bax expression. In multivariate analysis, only Bcl-2 expression, lymph node status, and histologic grade were of independent prognostic value with respect to RFS and OS. Because the vast majority of the patients in this study received chemotherapy, it can be concluded that these apoptotic markers were also predictive of response to chemotherapy. Immunostaining of apoptosis-related genes, Bcl-2 and Bax, together with AI, may stratify high- versus low-risk breast cancer patients.