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Axially chiral biaryls widely exist in natural products and pharmaceuticals and are used as chiral ligands and catalysts in asymmetric synthesis. Compared to the well-established axially chiral 6-membered biaryl skeletons, examples of 5-membered biaryls have been quite scarce, and mono-substituted 3-arylpyrrole atropisomers have not been reported. Here, we disclose a copper-catalyzed atroposelective diyne cyclization for the construction of a range of axially chiral arylpyrrole biaryls in good to excellent yields with generally excellent enantioselectivities via oxidation and X-H insertion of vinyl cations. Importantly, this protocol not only represents the first synthesis of mono-substituted 3-arylpyrrole atropisomers, but also constitutes the first example of atroposelective diyne cyclization and the first atropisomer construction via vinyl cations. Theoretical calculations further support the mechanism of vinyl cation-involved cyclization and elucidate the origin of enantioselectivity., (© 2023 Wiley-VCH GmbH.)

We investigated whether molecular subtype can predict the response and prognosis in Chinese locally advanced breast cancer (LABC) patients treated with preoperative therapy. LABC patients treated with preoperative therapy in Cancer Hospital, Fudan University between August 2001 and May 2008 were retrospectively analyzed. Molecular subtypes were constructed from the immunohistochemical results of hormonal receptors (HR) and HER2 status, which were classified as luminal (HR+/HER2-), triple negative (HR-/HER2-) and HER2 positive subtypes. Preoperative tumor parameters, chemotherapy regimens and response as well as outcome were compared among these subtypes. A total of 225 cases were included into analysis. Univariate and multivariate analysis showed that the pathological complete remission (pCR) independent predictive factors were molecular subtype and preoperative regimens. Compared with luminal subtype, patients with HER2 positive or triple negative tumor had significantly higher pCR rate, with odds ratio 3.02 (95% CI=1.07-8.07; P=0.037) and 3.10 (95% CI=1.01-9.52; P=0.048), respectively. However, HER2 positive or triple negative breast cancer patients were also associated with increased recurrence (P=0.072) and death rates (P=0.019) compared with luminal subtype in the whole population, and was especially worse in patients with residual disease after preoperative therapy with decreased disease-free survival (P=0.022) and overall survival (P=0.007). Our results show that molecular subtype can predict the response and prognosis of Chinese LABC patients treated with preoperative therapy. Compared with luminal subtype, patients with HER2 positive or triple negative disease had increased pCR rates, but associated with significantly worse survival, especially in those with residual disease after preoperative therapy.

Objective: To examine the effect of postoperative pregnancy upon the prognosis of young Chinese breast cancer patients., Methods: Four hundred and thirty-two female unilateral breast cancer patients aged 35 or younger were retrospectively reviewed. Kaplan-Meier analysis and Log Rank test were used for univariate analysis of factors predictive of disease-free survival (DFS) and overall survival (OS). Multivariate analysis was carried out using the Cox proportional hazards model., Results: Eighteen patients were identified to have postoperative pregnancy, including 5 full-term pregnancy and 13 abortions with the earliest pregnancy taking place at Month 17 post-operation. After a median follow-up of 62 months (6 - 237 months), the DFS and OS rates were 72.5% (313/432) and 88.7% (383/432) respectively. On multivariate analysis, postoperative pregnancy, clinical stage and number of pathologically involved axillary lymph node were significantly associated with DFS. And the axillary lymph node status was also predictive of OS. No death occurred in patient with postoperative pregnancy. There was no significant association between postoperative pregnancy and OS., Conclusion: Postoperative pregnancy has no adverse effect upon the prognosis of young breast cancer patients.

Objective: To identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen., Methods: One hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated., Results: All patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival., Conclusion: Pathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.

Objective: To investigate the relationship between breast cancer molecular classification and prognosis., Methods: From January 2002 to December 2003, 708 female primary breast cancer patients with a mean age of 53 years old were retrospectively analyzed. The classification of breast cancer was according to the immunohistochemical results of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status. Molecular classification definitions included highly endocrine responsive, incompletely endocrine responsive, triple negative, and HER2 positive. The prognosis among different molecular classifications of breast cancer was investigated. The survival rates of different classifications were compared by Log-rank test., Results: The proportion of highly endocrine responsive, incompletely endocrine responsive, HER2 positive and triple-negative breast cancer was 33.2% (235/708), 23.6% (167/708), 21.3% (151/708) and 21.9% (155/708). The follow-up period were from 3 to 68 months with a median of 40.2 months. A total of 100 cases were identified to had disease recurrence or death. Factors affecting the prognosis were tumor size, axillary lymph node status, molecular classification, adjuvant radiotherapy and adjuvant endocrine therapy by univariate analysis. Multivariate analysis revealed that the molecular classification and lymph node status were the independent prognostic factors with the hazard ratio 1.205 (P = 0.047) and 4.512 (P = 0.000), respectively. Survival analysis showed that highly endocrine responsive breast cancer was with superior prognosis versus others., Conclusions: Molecular classification of breast cancer is an independent predictor of prognosis. Breast cancer patients classified as highly endocrine responsive subtype have the best outcome.

Background: The purpose of this study was to evaluate retrospectively the efficacy and safety of neoadjuvant chemotherapy with vinorelbine-containing regimens in elderly patient with locally advanced breast cancer (LABC)., Patients and Methods: From 2002 to 2006, 14 female elderly patients with LABC underwent neoadjuvant chemotherapy with vinorelbine-containing regimens. Vinorelbine alone or in combination with pirarubicin/epirubicin was administered every 3 weeks (25 mg/m2, i.v., day 1 and day 8). All 14 patients received 2-6 cycles of chemotherapy., Results: The median age was 68.5 years (range 65 to 78 years). Six patients had stage IIIA breast tumor, 7 stage IIIB and 1 stage IIIC. There was 1 complete response and 10 partial responses, with an overall response rate of 78.57%, and stable disease in 3 patients (21.43%); there were no patients with progressive disease before surgery. After a median follow-up of 35 months, the estimated 3-year disease-free and overall survival rates were 57% and 69%, respectively., Conclusion: The results of the current study showed that vinorelbine-containing neoadjuvant chemotherapy was effective and well-tolerated in elderly patients with LABC.

Objective: To evaluate three biopsy methods which are currently used in stereotactic breast biopsy., Methods: A total of 361 cases of stereotactic breast biopsies were carried out since 2000, including 73 cases of true cut core needle biopsies (ST-CNB), 74 cases of vacuum assisted biopsies (ST-VAB) and 214 cases of excisional biopsies. After medium follow-up time of 18 months (6 to 66 months), the accuracy as well as the clinical benefits of the three stereotactic biopsy procedures were analyzed retrospectively., Results: The cancer miss rate of stereotactic wire localized excisional biopsy, ST-CNB and ST-VAB is 0, 2.7% and 0 respectively. Under-estimate rate of minimal invasive biopsy was 33% in atypical ductal hyperplasia (ADH) and 53% in ductal carcinoma in situ (DCIS). The minimal invasive procedure is superior to surgical procedure in terms of operation time, breast cosmetic outcome and complications, etc. Furthermore, 69% of the surgeries for suspicious lesion were waived., Conclusions: Stereotactic minimal invasive breast biopsy, especially ST-VAB, is an accurate, safty and convenient diagnosis technique and could be considered as the first line choice for mammographic moderate suspicious breast lesions (BIRADS-4). However, further excisional biopsy is recommended for atypical hyperplasia. Stereotactic excisional biopsy could be directly used for diagnosis of mammographic highly suspicious breast lesions (BIRADS-5).

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.