10-year changes and development of surgical treatment for breast cancer in China / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the changes and development of surgical treatment for breast cancer from 1999 to 2008 in China, and compare the differences between the surgical methods used in high-resource and low-resource areas.</p><p><b>METHODS</b>Clinicopathological data of surgical treatment for female primary breast cancer was collected via medical chart review at hospitals in seven geographic areas in China. Chi-square test and chisqure test for linear trends were used to analyze the changes and development of the surgical methods used for breast cancer in the 10 years.</p><p><b>RESULTS</b>A total of 4211 primary breast cancer patients were selected from the 10-year database, including 4078 women (97.5%) treated by surgical operation. Among 3271 women (80.21%) treated with modified radical mastectomy, the surgical rate was rising from 68.89% in 1999 to 80.17% in 2008, ascending by 11.28% (χ(2) = 31.143, P < 0.001). In high-resource areas, the surgical rate of modified radical mastectomy was rising from 45.64% in 1999 to 76.13% in 2008, ascending by 30.49% (χ(2) = 89.393, P < 0.001), while in low-resource areas it kept a steady rate at 80% in the ten years (χ(2) = 2.113,P = 0.146). Among 231 women (5.66%) treated with breast-conserving surgery, the surgical rate was rising from 1.29% in 1999 to 11.57% in 2008, ascending by 10.28% (χ(2) = 102.835, P < 0.001). In high-resource areas, the surgical rate of breast-conserving surgery was rising from 2.68% in 1999 to 16.87% in 2008, ascending by 14.19% (χ(2) = 69.544, P < 0.001), while in low-resource areas it was rising from 0.42% in 1999 to 6.22% in 2008, ascending by 5.80% (χ(2) = 30.003, P < 0.001). Among 469 women (11.50%) treated with Halsted radical mastectomy, the surgical rate was declining from 28.28% in 1999 to 4.96% in 2008, descending by 23.32% (χ(2) = 206.202, P < 0.001). In high-resource areas, the surgical rate of Halsted radical mastectomy was declining from 50.34% in 1999 to 3.29% in 2008, descending by 47.05% (χ(2) = 274.830, P < 0.001), while in low-resource areas it was declining from 14.58% in 1999 to 6.64% in 2008, descending by 7.94% (χ(2) = 8.166, P = 0.004). Among 3786 women treated with breast mastectomy (including modified radical mastectomy and Halsted radical mastectomy), the surgical rate was declining from 98.46% in 1999 to 86.36% in 2008, descending by 12.10% (χ(2) = 95.744, P < 0.001). In high-resource areas, the surgical rate of breast mastectomy was declining from 96.64% in 1999 to 80.66% in 2008, descending by 15.98% (χ(2) = 53.446, P < 0.001), while in low-resource areas it was declining from 99.58% in 1999 to 92.12% in 2008, descending by 7.46% (χ(2) = 36.758,P < 0.001).</p><p><b>CONCLUSIONS</b>The main primary surgical treatment for breast cancer is modified radical mastectomy during the period 1999 - 2008. Halsted radical mastectomy is gradually replaced by modified radical mastectomy and breast-conserving surgery. The rate of changes for breast-conserving surgery and mastectomy is higher in high-resource areas than that in low-resource areas. Breast-conserving surgery will become the main treatment for early-stage breast cancer.</p>

Polymorphisms of GSTP1 is associated with differences of chemotherapy response and toxicity in breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.</p><p><b>METHODS</b>One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.</p><p><b>RESULTS</b>Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs.</p><p><b>CONCLUSION</b>GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.</p>

Comparison of touch imprint cytology of core needle biopsy and section histopathology in breast cancer diagnosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the sensitivity, specificity of touch imprint cytology (TIC), and to compare its conformity rate with histopathology, to observe the consistence of immunocytochemistry (ICC) with immunohistochemistry (IHC), and to assess the diagnostic value of TIC prior to neoadjuvant chemotherapy for breast cancer.</p><p><b>METHODS</b>289 cases of TIC and 287 cases with core needle biopsy (CNB) histopathology accumulated from October 2005 to October 2008 in our hospital were included in this study. One hundred ninety cases TIC results were compared with that of final histopathology. 64 cases were tested for ER, PR, HER-2 by immunocytochemistry.</p><p><b>RESULTS</b>Twenty-four benign cases and 263 malignant cases were diagnosed. 4 specimens were unsatisfactory. False negative rate and unsatisfactory rate were 1.4%, both, and false positive rate was 0.35%. The accuracy rate of TIC and CNB was 95.8% and 95.3%, respectively (P = 0.804). The sensitivity of TIC and CNB was 96.2% and 95.0% (P = 0.601), specificity 87.5% and 100% (P = 0.471) were found, when compared with the results of routine histopathology. 52 cases had a control with IHC of CNB in 64 ICC, and 43 cases had a final histopathology IHC. The ICC conformity rate of ER, PR, HER-2 with IHC of CNB was 86.5%, 75.0%, 78.8%, and that with IHC of final histopathology was 88.4%, 74.4%, 75.6%, respectively. The conformity rate of IHC between CNB and final histopathology was 83.7%, 74.4%, 76.5%, respectively. There was no significant statistical difference between them.</p><p><b>CONCLUSION</b>Compared with routine CNB histopathology, TIC has a high accuracy and sensitivity, and can provide a rapid and reliable cytological diagnosis to complement CNB for breast lesions. The conformity rates are high in ER, PR, HER-2 expression between ICC and IHC. ICC of TIC can be used to determine the estrogen and progesterone receptor levels in breast cancer before neoadjuvant chemotherapy.</p>

Clinical characteristics and survival in the operable breast cancer patients with different molecular subtypes / 中华肿瘤杂志

<p><b>OBJECTIVE</b>According to the immunohistochemical (IHC) test of ER, PR and HER-2, breast cancer can be divided into 4 different molecular subtypes: Luminal A subtype (ER or PR positive and HER-2 negative), Luminal B subtype (ER or PR positive and HER-2 positive), HER-2 subtype (ER and PR negative, HER-2 positive) and Basal-like subtype (ER, PR and HER-2 negative). This study was to analyze the clinical features of different breast cancer subtypes, and try to find the evidence of combined and individualized treatment for patients with breast cancer.</p><p><b>METHODS</b>The data of 408 surgically treated breast cancer patients in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2002 to December 31, 2002 were collected and retrospectively analyzed. The clinicopathological features and recurrence, metastasis as well as survival of these four subtypes were compared.</p><p><b>RESULTS</b>Of the 408 cases, Luminal A subtype accounted for 60.8% (248/408), Luminal B subtype 7.8% (32/408), HER-2 subtype 12.5% (51/408), and Basal-like subtype 18.9% (77/408). Basal-like subtype had less lymph node metastases than other subtypes (P<0.05). HER-2 subtypes consisted of less patients aged 45 years or younger than other subtypes (P<0.05). Luminal B subtype contained less advanced cases than other subtypes (P<0.01). By August 2008, the median time of follow-up was 64 months (range, 3-79 months). Fifty-eight cases presented local recurrence or metastasis, and 51 of them died of the disease. The 5-year overall survival rates (OS) for patients with Luminal A, Luminal B, Basal-like and HER-2 subtype were 89.83%, 86.15%, 79.85% and 86.70% , respectively. The 5-year disease-free survival (DFS) rates of the four subtypes were 83.52%, 68.88%, 71.66% and 75.83%, respectively. The rate of local recurrence or metastasis in Luminal A subtype was significantly lower than that in Luminal B and Basal-like subtypes (P<0.05). The DFS time in Luminal B subtype was shorter than that in Luminal A subtype (P=0.0481). The OS and DFS time in Basal-like subtype were all shorter than that in Luminal A subtype (P=0.0077 and P=0.0306, respectively).</p><p><b>CONCLUSION</b>The distribution of each subtype in Chinese breast cancer patients is similar to that in European and American breast cancer patients. Luminal A is the most common subtype in Chinese breast cancer patients, and has a good prognosis. While Basal-like and Luminal B subtype have a poor prognosis.</p>

Clinical characteristics comparison between triple-negative and non-triple-negative breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the clinical characteristics of triple-negative (TN) breast cancer and non-triple-negative (NTN) breast cancer, enrich the information of TN patients, and provide evidences for individualized combined treatment.</p><p><b>METHODS</b>The data of 408 cases received operation in the year of 2002 was enrolled in this study. TN patients were confirmed according to the immunohistochemical (IHC) test of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu. The clinical characteristics, recurrence, metastasis and survival were compared between the two groups.</p><p><b>RESULTS</b>Seventy-seven patients (18.9%) were confirmed TN cases. The median follow-up was 64 months (range, 3-79 months). Of all the cases, 58 occurred local recurrence or metastasis and 51 died, it was 19 and 12 in TN group. Compared with the NTN group, the TN patient tended to be younger and the tumor mass larger (P=0.015 and 0.011). However, axillary lymph nodes metastasis occurred more often in NTN patients than in TN patients (P=0.001). The rate of local recurrence and metastasis in TN group was significantly higher than in NTN group (P=0.005 and 0.025), and TN cases were more likely to develop lung metastasis than NTN patients (P<0.01). The 3-year and 5-year overall survival rate in TN group were significantly lower than in NTN group (86.4% vs. 93.4%, P=0.0205; 77.7% vs. 87.9%, P=0.0215). The 3-year and 5-year disease-free survival rate in TN group were also significantly lower than in NTN group (78.4% vs. 92.4%, P=0.0038; 72.8% vs. 85.8%, P=0.0041). Tumor size, lymph node status and triple-negative were the most important factors influencing the prognosis on multivariate Cox regression analysis.</p><p><b>CONCLUSIONS</b>TN breast cancer haa some specific clinical characteristics. The prognosis of TN patients is worse than that of NTN patients. Further study is needed to find individualized treatment for TN breast cancer patients.</p>

A comparison of localization by ductoscopy-guided wire and conventional methods in terminal duct excision for women with pathological nipple discharge / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate and compare localization by ductoscopy-guided wire with localization by conventional methods in the terminal duct excision for women with pathological nipple discharge.</p><p><b>METHODS</b>Breast terminal duct excision were performed in 174 consecutive patients with intraductal lesions diagnosed by mammary ductoscopy. Sixty-eight of those underwent ductoscopy-guided wire localization for more accurate ductal excision. The patients received mammary ductoscopy and a hooked wire was anchored at the intraductal lesions under endoscopic surveillance just before the operation. Then a biopsy resection of wire-guided terminal duct and frozen section were done. Tbe other 106 patients received terminal duct excision under localization with conventional methods without ductoscopy either by puncturing a needle or injection of blue dye through the duct with pathological discharge.</p><p><b>RESULTS</b>Of the 68 patients with ductoscopy-guided duct excision, 64 had intraductal papillomas and 4 duct carcinoma in situ proved by pathology. All the lesions in these 68 patients were completely resected during biopsy without extra extended resection, and the concordance rate of the pathological result with ductoscopic diagnosis was 100.0%. None of them developed a postoperative breast distortion. In the conventional method localization group, there were 96 intraductal papilloma, 6 duct carcinoma in situ and 4 adenosis. Only 77.4% of the lesions were excised in the primary biopsy, and 22.6% needed extended resection. The concordance rate of the pathological diagnosis with ductoscopic diagnosis was 96.2%. Twenty-six patients had a deformed breast postoperatively.</p><p><b>CONCLUSION</b>Ductoscopy-guided wire localization is superior to the conventional localization method in the surgical terminal duct excision for women with spontaneous nipple discharge. It is not only helpful for more accurate localization and resection as well as pathologic sampling, but also is minimally invasive. Further studies are still required and this method may deserve to be popularized.</p>

Detection of micrometastases in sentinel lymph nodes of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate an optimal examination method to detect micrometastases in sentinel lymph nodes (SLNs) of breast cancer.</p><p><b>METHODS</b>Firstly, the SLNs of breast cancer were found by 99mTc-DX isotope method. Secondly, all the SLNs which were negative by routine HE examination were serially sectioned at a 100 microm interval and stained by both HE and immunohistochemistry for detecting micrometastases. All tumor tissue paraffin blocks were also sectioned and stained with HE and immunohistochemistry as control.</p><p><b>RESULTS</b>Totally, 121 SLNs and 44 tumors of 59 patients were examined. Micrometastasis was found to be positive in 17 SLNs (14.0%) of 14 patients (23.7%). When examined number of sections was increased from one to three, more positive micrometastatic SLNs were detected by HE staining only (3, 7, 10 for 1, 2, 3 sections, respectively). When HE staining was combined with immunohistochemical staining for AE1/3 or CK19 or muc1, much more positive micrometastatic SLNs were found (14, 12, 16 for 1, 2, 3 sections, respectively). The more sections were examined, the more micrometastases in SLNs were found. Furthermore, micrometastasis was also found to be positively correlated with the tumor size and the expression of c-erbB2, MMP-2, VEGF. The larger the tumor size was or the stronger expression of the above mentioned biomarkers, the more micrometastases in SLNs could be found.</p><p><b>CONCLUSION</b>Serially sections at a 100 microm interval and staining with both HE and immunohistochemical technique using muc1 antibody may be the best way to detect micrometastases in sentinel lymph nodes in breast cancer patients.</p>

A prospective multicenter clinical trial of breast conserving therapy for early breast cancer in China / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To demonstrate the feasibility of breast conserving therapy (BCT) and establish a multimodality BCT model for early breast cancer in China.</p><p><b>METHODS</b>A prospective multicenter case control study consisting of 4461 patients was carried out by the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and nine other hospitals across China from November, 2001 to November, 2004, the result of BCT and mastectomy on early stage breast cancer were compared. Patients entry-primary tumor < or = 3 cm, primary tumor in periphery quadrant, pathology showed infiltrating carcinoma and clinical absence of locoregional lymphatic or distant metastasis. Patients rejection-multiple center cancer or diffused malignant calcified spots, previous radical radiation therapy in the chest, accompanying collogenolytic vascular granuloma and simultaneous pregnancy.</p><p><b>RESULTS</b>Of these 4461 patients, breast conserving surgery was performed in 872 (19.5%) patients who were eligible for BCT, accounting for 9.0% of all operated breast cancer patients during the same period. The rates of local recurrence, metastasis and death were 1.0% (9/872), 1.3% (11/872) and 0.1% (1/872) in BCT group, versus 0.5% (18/3589), 1.4% (49/3589) and 0.1% (4/3589) in the mastectomy group. No statistical significant difference was found between these two groups (P > 0.05). Cosmetic evaluation of breast in BCT group was carried out postoperatively at points of six months, one year and two years with 89.7%, 91.1% and 86.6% of the patients assessed as excellent or fine cosmetic state respectively.</p><p><b>CONCLUSION</b>Breast conserving therapy for early stage breast cancer is feasible in China, with no ominous effect on the survival and recurrence rate. Breast conserving therapy is able to improve not only the quality of life but also enhance the confidence of the patients, in addition to quasi-perfect cosmetic results. Standard comprehensive BCT involving multi-centers all concentrating on combination treatment should be widely adopted in China in the future. However, breast conserving surgery should selectively be used only for early stage breast cancer, and should be combined with postoperative radiotherapy, chemotherapy and hormone therapy in order to guarantee success.</p>

Bilateral primary breast cancer: a report of 217 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To report the clinical and pathological characteristics of bilateral primary breast cancer (BPBC) in comparison with unilateral primary breast cancer (UPBC).</p><p><b>METHODS</b>A retrospect database of primary breast cancer patients admitted to the Cancer Hospital from March 1967 through May 2003 was analyzed.</p><p><b>RESULTS</b>A total of 10,470 primary breast cancer patients were treated, among which 271 patients had bilateral primary tumors with an incidence of 2.1%. Most of the BPBC, developed both synchronously (sBPBC, incidence rate: 0.6%) and metachronously (mBPBC, incidence rate: 1.5%), were diagnosed in premenopausal women with an average age of 48. In the latter cases, the median time interval between their occurrences was 57.6 months. The median survival time for patients with sBPBC and mBPBC was 29.6 months and 27.8 months, respectively. There was no statistical difference in survival rate between the 2 groups of patients. Nor was menopausal status related to survival. In mBPBC patients, when the occurrence of the second breast cancer was taken as the beginning of prognostic analysis, the prognosis of BPBC patients was worse than those with unilateral involvement.</p><p><b>CONCLUSION</b>Prognosis of patients with bilateral primary breast cancer is poor. In mBPBC patients whose breast cancers appear one after the other, meticulous follow-up is needed after resection of tumor on one side to early detect development of cancer of the countralateral breast especially within 5 years.</p>

Clinicopathologic analysis of primary pure squamous cell carcinoma of the breast / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic characteristics and treatment method for primary pure squamous cell carcinoma of the breast.</p><p><b>METHODS</b>Twelve patients with primary squamous cell carcinoma of the breast pathologically confirmed were retrospectively reviewed. The clinical characteristics, diagnosis, treatment and prognosis were analyzed.</p><p><b>RESULTS</b>All 12 patients were women with median age of 50 years (44-76 years). The patients all presented a single mass in the breast on presentation. The diameter ranged from 2.5 cm to 10.0 cm in diameter. All of the patients had undergone surgical resection. There were 6 cases in stage IIa, 2 in IIb, 2 in IIIa and 2 in IIIb according to the TNM staging system of AJCC and UICC. Ten of the 12 cases were followed-up from 4 months to 189 months.</p><p><b>CONCLUSION</b>Primary squamous cell carcinoma of the breast is often in need of diagnosis by exclusion, but can be initially confirmed by fine needle aspiration. Presently, no standard therapy can be recommended in practice. The prognosis is controversial.</p>