Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer.

INTRODUCTION: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond. METHODS: This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication. RESULTS: Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3- 9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities. CONCLUSIONS: In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.

Evaluation of the prognostic value of 2005 St Gallen risk categories for operated breast cancers in Hong Kong.

Incorporating various new and conventional risk factors, the 2005 St Gallen risk categorization is a potentially useful prognostic tool for breast cancers. We conducted a retrospective study to evaluate its application in Hong Kong. Of the 902 included female breast cancers with median follow-up of 5.4 years, 7%, 63% and 30% patients were classified as low-, intermediate- and high-risk categories, respectively. Their corresponding 5-year distant disease-free survivals (DDFS) were 100%, 92% and 72%, respectively (p<0.00005). In the intermediate-risk category, node-positive patients had marginally inferior 5-year DDFS than node-negative patients (89% vs. 93%, p=0.0551). In the high-risk category, patients having HER2 overexpressed tumors and 1-3 positive nodes had significantly better DDFS than other patients with > or = 4 positive nodes (89% vs. 65%, p=0.0001). Overall, the 2005 St Gallen risk categorization had high prognostic value. However, the impact of HER2 overexpression might be affected by reproducibility of HER2 tests.

Surveillance mammography after breast conservation therapy in Hong Kong: effectiveness and feasibility of risk-adapted approach.

Annual surveillance mammography is commonly recommended after breast conservation therapy (BCT). We retrospectively reviewed its effectiveness on 511 invasive and non-invasive breast cancers treated with BCT between 1994 and 2003. The median follow-up was 5.9 years. The 5-year actuarial ipsilateral breast tumour recurrence (IBTR) rate was 4.5% and contralateral breast cancer (CBC) rate was 2.0% (representing eight times increase in risk). IBTR of 43% and 62% CBC were first detected by surveillance mammography. The IBTR detection rates per 1000 mammograms were 5.2 for patients (n=349) with one or more IBTR risk factors (age 45, positive/close margins or histological grade 3) and 0.6 for patients (n=162) without. No survival difference was observed between different modes of IBTR detection (p=0.342). In conclusion, a risk-adapted approach of limiting ipsilateral surveillance to patients with IBTR risk is possible but its implementation will be complicated by the continued need of contralateral surveillance.

Wide local excision and radiotherapy for the treatment of ductal carcinoma in situ of the breast: the Hong Kong experience.

AIMS: Breast conservation treatment for ductal carcinoma in situ (DCIS) was unpopular in the Chinese population and the outcome was seldom reported. We conducted a single-centre retrospective study to examine the clinical outcome of women in Hong Kong. MATERIALS AND METHODS: Seventy-five Chinese women were treated with wide local excision and radiotherapy for DCIS of the breast between 1994 and 2003. Only 26 (34.7%) women had non-palpable DCIS detected by screening mammograms. All women were treated with whole breast irradiation of 50 Gy in 2 Gy daily fractions, with 50 (66.7%) women receiving an additional electron boost of 10-16 Gy. RESULTS: The median follow-up was 5.1 years (range 2.0-10.7). At the last assessment, four women developed local recurrences, but all remained disease-free after salvage mastectomy. The 5-year actuarial local failure-free rate and cause-specific survival rate were 92.9% (95% confidence interval 89.4-96.4) and 100.0%, respectively. Cosmetic results were rated as good to excellent in all women. On univariate analysis of prognostic factors for local failure, only a close (< or = 2 mm) final resection margin approached statistical significance (hazard ratio 9.108; 95% confidence interval 0.946-87.655; P = 0.056). The 5-year actuarial local failure-free rates for women with a close (< or = 2 mm) final resection margin and women with wider margins were 77.0 and 98.2%, respectively. CONCLUSIONS: Despite geographical and demographic differences, the clinical outcome after wide local excision and radiotherapy for DCIS of the breast in Chinese women is comparable with that in Western series. Efforts are needed to achieve cosmetically acceptable tumour-free margins greater than 2 mm.

Post-mastectomy radiotherapy after immediate autologous breast reconstruction in primary treatment of breast cancers.

AIM: To assess the clinical outcome of breast cancer patients with immediate autologous breast reconstruction and post-mastectomy radiotherapy (PMRT) as primary treatment. MATERIALS AND METHODS: Twenty-five women with breast cancer treated with immediate autologous breast reconstruction and post-mastectomy radiotherapy as primary treatment between 1995 and 2001 in Pamela Youde Nethersole Eastern Hospital of Hong Kong were retrospectively studied. Radiation doses of 50 Gy (in 2 Gy daily fraction) were given to the reconstructed breasts, except one who was given 45 Gy (in 1.8 Gy daily fraction). Nine women (36%) were treated without bolus, whereas the other 16 women (64%) were treated with 0.5 cm thick bolus on alternate days. The main outcome measures include local control, treatment complications and cosmetic outcome. RESULTS: Median follow-up was 3.7 years (range: 1.0-6.6 years). Two women (8%), who were treated without bolus, developed chest wall recurrences. The overall 5-year, actuarial, local failure-free rate and disease-specific survival rate were 89.8% and 77.9%, respectively. Apart from mild acute skin reactions, no significant acute radiotherapy side-effects were observed. No flap necrosis or flap loss was seen. The cosmesis of the reconstructed breasts were rated as good to excellent in 85% of the surviving patients. There was no observed adverse effect on cosmesis by adding bolus on alternate days. CONCLUSION: PMRT after immediate autologous tissue-flap breast reconstruction is well tolerated and is not associated with increased incidence of complications. Adding 0.5 cm bolus on alternate days might improve local control without causing adverse cosmetic effect. The concern of adverse effects of radiotherapy should not exclude the choice of immediate breast reconstruction in suitable patients.