Update on the Recommendations on Breast Cancer Screening by the Cancer Expert Working Group on Cancer Prevention and Screening.

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population: Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening. A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-ß/SMAD4 signaling.

Recent evidence from a comprehensive genome analysis and functional studies have revealed that FOXM1 is a crucial metastatic regulator that drives cancer progression. However, the regulatory mechanism by which FOXM1 exerts its metastatic functions in cancer cells remains obscure. Here, we report that DLX1 acts as a FOXM1 downstream target, exerting pro-metastatic function in ovarian cancers. Both FOXM1 isoforms (FOXM1B or FOXM1C) could transcriptionally upregulate DLX1 through two conserved binding sites, located at +61 to +69bp downstream (TFBS1) and -675 to -667bp upstream (TFBS2) of the DLX1 promoter, respectively. This regulation was further accentuated by the significant correlation between the nuclear expression of FOXM1 and DLX1 in high-grade serous ovarian cancers. Functionally, the ectopic expression of DLX1 promoted ovarian cancer cell growth, cell migration/invasion and intraperitoneal dissemination of ovarian cancer in mice, whereas small interfering RNA-mediated DLX1 knockdown in FOXM1-overexpressing ovarian cancer cells abrogated these oncogenic capacities. In contrast, depletion of FOXM1 by shRNAi only partially attenuated tumor growth and exerted almost no effect on cell migration/invasion and the intraperitoneal dissemination of DLX1-overexpressing ovarian cancer cells. Furthermore, the mechanistic studies showed that DLX1 positively modulates transforming growth factor-ß (TGF-ß) signaling by upregulating PAI-1 and JUNB through direct interaction with SMAD4 in the nucleus upon TGF-ß1 induction. Taken together, these data strongly suggest that DLX1 has a pivotal role in FOXM1 signaling to promote cancer aggressiveness through intensifying TGF-ß/SMAD4 signaling in high-grade serous ovarian cancer cells.

The interaction between C35 and ΔNp73 promotes chemo-resistance in ovarian cancer cells.

BACKGROUND: The purpose of this study was to characterise the oncogenic roles of C35, a novel protein binding partner of ΔNp73, in ovarian cancer and to investigate the functional significance of C35-ΔNp73 interaction in the regulation of chemo-resistance. METHODS: C35 expression was evaluated by quantitative real-time PCR in human ovarian cancer tissues and cell lines. The aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell proliferation, migration, soft agar and nude mouse xenograft. The significance of C35-ΔNp73 interaction in chemo-resistance was evaluated by apoptosis assays and cell viability after cisplatin treatment. RESULTS: The expression of C35 was significantly enhanced in human ovarian cancer tissues. Overexpression of C35 augmented proliferation, migration and tumourigenicity in ovarian cancer cell lines. C35 knockdown inhibited cell motility and cell growth. The co-expression of C35 and ΔNp73 by transient or stable transfection in ovarian cancer cells induced greater resistance to cisplatin treatment than did transfection with C35 or ΔNp73 alone. The cisplatin resistance was demonstrated to be caused by increased AKT and NFκB activity induced by C35-ΔNp73. CONCLUSION: Our results suggest that ΔNp73 might cooperate with C35 to promote tumour progression and contribute to cisplatin resistance in ovarian cancer cells. Future studies of the functional roles of ΔNp73 and C35 will provide insight that will aid in the establishment of new strategies and more effective therapies.

Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers.

Ovarian cancer is the most lethal of all gynecological malignancies, and the identification of novel prognostic and therapeutic targets for ovarian cancer is crucial. It is believed that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. NANOG is one of the key transcription factors essential for maintaining self-renewal and pluripotency in stem cells. This study investigated the role of NANOG in ovarian carcinogenesis and showed overexpression of NANOG mRNA and protein in the nucleus of ovarian cancers compared with benign ovarian lesions. Increased nuclear NANOG expression was significantly associated with high-grade cancers, serous histological subtypes, reduced chemosensitivity, and poor overall and disease-free survival. Further analysis showed NANOG is an independent prognostic factor for overall and disease-free survival. Moreover, NANOG was highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Stable knockdown of NANOG impeded ovarian cancer cell proliferation, migration and invasion, which was accompanied by an increase in mRNA expression of E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1. Conversely, ectopic NANOG overexpression enhanced ovarian cancer cell migration and invasion along with decreased E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1 mRNA expression. Importantly, we found Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. This is the first report revealing the association between NANOG expression and clinical outcome of patients with ovarian cancers, suggesting NANOG to be a potential prognostic marker and therapeutic molecular target in ovarian cancer.

The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring.

BACKGROUND: This study aimed to evaluate traditional Chinese medicine (TCM) in improving quality of life (QOL), reducing chemotoxicity and modulating immune function in patients undergoing chemotherapy. PATIENTS AND METHODS: Patients with ovarian cancer were randomized to receive either TCM or placebo in addition to standard chemotherapy. The primary outcome was global health status (GHS) score, assessed by European Organization for Research and Treatment of Cancer questionnaire, while the secondary outcomes were other QOL items, chemotoxicity according to World Health Organization criteria and alterations in immune function as measured by immune cells count and the numbers of cytokines-secreting cells. RESULTS: There was no significant difference in the GHS between the two groups. With adjustment for stage, chemotherapy type, disease status, age and baseline value, emotional function, cognitive function and nausea and vomiting were found to be worse or less improved in the TCM group compared with placebo group after six cycles of chemotherapy. The TCM group had less neutropenia after three cycles (0% grade 4 neutropenia versus 28.6%). There were no other significant differences in terms of chemotoxicity. Lymphocyte counts and cytokine activities decreased less in the TCM group. CONCLUSIONS: TCM did not improve QOL but did have some effects in terms of maintaining immune function.

Iron supplement in pregnancy and development of gestational diabetes--a randomised placebo-controlled trial.

OBJECTIVE: To test the hypothesis that iron supplement from early pregnancy would increase the risk of gestational diabetes mellitus (GDM). DESIGN: Randomised placebo-controlled trial. SETTING: A university teaching hospital in Hong Kong. POPULATION: One thousand one hundred sixty-four women with singleton pregnancy at less than 16 weeks of gestation with haemoglobin (Hb) level between 8 and 14 g/dl and no pre-existing diabetes or haemoglobinopathies. METHODS: Women were randomly allocated to receive 60 mg of iron supplement daily (n= 565) or placebo (n= 599). Oral glucose tolerance tests (OGTTs) were performed at 28 and 36 weeks. Women were followed up until delivery. OUTCOME MEASURES: The primary outcome was development of GDM at 28 weeks. The secondary outcomes were 2-hour post-OGTT glucose levels, development of GDM at 36 weeks and delivery and infant outcomes. RESULTS: There was no significant difference in the incidence of GDM in the iron supplement and placebo groups at 28 weeks (OR: 1.04, 95% confidence interval [CI]: 0.7-1.53 at 90% power) or 36 weeks. Maternal Hb and ferritin levels were higher in the iron supplement group at delivery (P < 0.001 and P= 0.003, respectively). Elective caesarean section rate was lower in the iron supplement group (OR: 0.58, 95% CI: 0.37-0.89). Infant birthweight was heavier (P= 0.001), and there were fewer small-for-gestational-age babies in the iron supplement group (OR: 0.46, 95% CI: 0.24-0.85). CONCLUSION: Iron supplement from early pregnancy does not increase the risk of GDM. It may have benefits in terms of pregnancy outcomes.

Acceptability of human papillomavirus vaccination among Chinese women: concerns and implications.

OBJECTIVE: To explore Chinese women's perceptions of human papillomavirus (HPV) vaccination and their intention to be vaccinated. DESIGN: A cross-sectional community-based survey study. SETTING: Thirteen community women's health centres of The Family Planning Association of Hong Kong. SAMPLE: A total of 1450 ethnic Chinese women aged 18 or above who attended the health centres. METHODS: Participants completed a written consent and an anonymous questionnaire onsite. MAIN OUTCOME MEASURES: Knowledge and beliefs about HPV and HPV vaccination against cervical cancer and participants' own intention to be vaccinated. RESULTS: About 38% of the participants (n = 527) had heard of HPV and 50% (n = 697) had heard of vaccination against cervical cancer. HPV infection was perceived to be stigmatising and detrimental to intimate, family and social relationships. Despite misconceptions and a grossly inadequate knowledge about HPV and HPV vaccination, 88% of the participants (n = 1219) indicated that they would likely be vaccinated. Majority of the participants believed that sexually experienced women should be vaccinated, while 27% opposed vaccinating sexually naive women. Younger age women who perceived a disruptive impact of HPV infection on intimate relationship and their partners' approval were significantly associated with a positive intention to be HPV vaccinated. CONCLUSIONS: The easy acceptability of HPV vaccination among the mostly sexually experienced Chinese participants and their knowledge deficit on the subject may implicate potential misuse of the vaccines and a false sense of security against cervical cancer. There is a dire need for culturally sensitive and tailored education for the public, women of different ages and their partners about HPV and HPV vaccination. Emphasis must be placed on the prophylactic nature of the current vaccines, the uncertain effects when given to sexually experienced women, the importance of adolescent vaccination and the need for continued cervical screening whether vaccinated or not.

The role of regular physical examination in the detection of ovarian cancer recurrence.

OBJECTIVE: To evaluate how ovarian recurrences were first detected and the relative role of Ca 125, symptom enquiry and physical examination in recurrence detection. METHODS: In this retrospective study, records from women with ovarian cancer recurrences diagnosed between 1999 and 2004 were reviewed to determine how the recurrences were first detected. Women were routinely followed up by a combination of symptom enquiry, physical examination and Ca 125. When recurrence was suspected, further investigations such as imaging and biopsy of the suspected recurrence would be arranged to confirm the diagnosis. The patients were followed up for a median of 53.5 months. RESULTS: Eighty patients were identified to have ovarian cancer recurrences, with median time to recurrence of 12 months. Although 41 (51%) had abnormal physical findings, only three (3.8%) first presented with physical findings and none had positive physical findings alone. Ca 125 taken at the clinic visits in these 3 patients when the signs were detected turned out to be raised. For the remaining 77 patients, 49 (61%) and 28 (35%) first presented with raised Ca 125 level and symptoms respectively. The median survival from the time of recurrence for those first presented with Ca 125, symptoms and physical findings were 25 months, 17 months and 11 months respectively. CONCLUSION: Routine physical examination had a very limited additional role and could be possibly omitted as part of the routine follow up strategy.

Barriers and facilitators to human papillomavirus vaccination among Chinese adolescent girls in Hong Kong: a qualitative-quantitative study.

OBJECTIVES: To explore perceptions towards cervical cancer, human papillomavirus (HPV) infection and HPV vaccination and to identify factors affecting the acceptability of HPV vaccination among Chinese adolescent girls in Hong Kong. METHODS: Six focus groups were conducted with Chinese adolescent girls (median age 16 years, age range 13-20, n = 64) in Hong Kong in April 2007. Thematic analysis was employed to identify major themes related to cervical cancer and HPV vaccination. A supplementary questionnaire was administered to all participants before and after group discussion to assess their knowledge, attitudes and intention to be vaccinated and to collect demographic information. RESULTS: Participants' knowledge on cervical cancer was limited and HPV was largely unheard of. They had difficulty understanding the mechanism linking cervical cancer with HPV infection. Participants held a favourable attitude towards HPV vaccination but the perceived timing of vaccination varied. Barriers to vaccination include high monetary cost, uncertain length of vaccine effectiveness, low perceived risk of HPV infection, no immediate perceived need of vaccination, anticipated family disapproval and fear of the pain of injection. Factors conducive to vaccination include perceived family and peer support and medical reassurance on safety and efficacy of vaccine. The differences on knowledge, attitudes, intention to be vaccinated now and willingness to conform to significant others before and after the discussion were statistically significant, with an increased tendency towards favouring vaccination after the focus group. CONCLUSIONS: Participants favoured HPV vaccination despite not feeling an immediate need to be vaccinated. Interventions could focus on providing professional information on HPV vaccination and raising adolescents' perceived need to take preventive measures against HPV infection.

A combination of chemoirradiation and chemotherapy for treatment of advanced clear cell adenocarcinoma of the cervix.

Clear cell adenocarcinoma of the cervix (CCAC) is an uncommon tumor. No good treatment option has been reported for advanced disease, and the prognosis is generally poor. We report a case of a 14-year-old girl with stage III CCAC. She was given whole-pelvic external irradiation (40 Gy in 20 daily fractions) and high-dose rate brachytherapy with concurrent weekly cisplatin (40 mg/m(2)), followed by further external irradiation to the parametria with central shield (14 Gy in seven daily fractions). She then received one cycle of carboplatin (area under the curve [AUC] 6) with paclitaxel (175 mg/m(2)) and two cycles of carboplatin (AUC 4) with gemcitabine (1000 mg/m(2) on days 1 and 8) because she developed anaphylactic shock to paclitaxel. Chemotherapy was stopped after the third cycle due to initial poor general condition. However, she gradually improved while on palliative care. Reassessment 6 months later showed no evidence of residual disease, and she remained disease free during a follow-up of 1 year. The complete response in this case suggests that chemoirradiation followed by combination chemotherapy may be a treatment option for advanced CCAC.

The use of vaginal antimicrobial after large loop excision of transformation zone: a prospective randomised trial.

OBJECTIVE: To investigate whether the use of an antibacterial vaginal pessary containing tetracycline and amphotericin B would reduce complications from large loop excision of the transformation zone (LLETZ). DESIGN: Prospective randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, University of Hong Kong. POPULATION: A total of 321 women who underwent LLETZ. METHODS: Women were randomised to either receiving an antimicrobial vaginal pessary twice a day for 14 days after LLETZ or no medication. Before LLETZ, endocervical and high vaginal swabs were taken for the detection of Chlamydia and other pathogens. All women were given a diary to record the degree of symptoms, such as vaginal discharge, bleeding and pain for 3 weeks. These were then compared between the two groups. MAIN OUTCOME MEASURES: Bleeding, vaginal discharge and pain after LLETZ. RESULTS: There was no significant difference in the total bleeding, vaginal discharge and pain scores between the two groups. However, for women who had positive endocervical or high vaginal swabs, the treatment group had significantly less bleeding in the second week (Z=-2.083, P= 0.037) and less overall vaginal discharge (Z=-2.024, P= 0.043). CONCLUSIONS: An antimicrobial vaginal pessary containing tetracycline and amphotericin B did not provide any significant benefit after LLETZ, except for a subgroup of women with positive vaginal or endocervical swabs. Given that this group of women cannot be identified before the procedure since swabs are not routinely taken, the use of routine prophylactic topical antibiotics cannot be recommended for the general population.

Nutritional intake and placental size in gestational diabetic pregnancies--a preliminary observation.

A disproportionately large placenta may represent an adaptive response to adverse intrauterine conditions. Both maternal nutritional intake and presence of gestational diabetes (GDM) have been found to affect relative placental growth. As dietary modification is part of the standard management in GDM women, the observed increase in placental size in these women may be partly due to dietary modification. In this study, we set out to examine the relationship between dietary intake and placental size in GDM pregnancies. Food diaries for five consecutive days for 52 women diagnosed with GDM were obtained to assess their nutritional intake in terms of total calories, carbohydrate, protein and fat. Spearman's correlations were calculated for nutritional intake and various factors that may correlate with placental weight. There was a significant inverse relationship (P=0.021) between placental weight and protein intake. No correlations with the other two nutritional components could be demonstrated. Maternal nutritional intake was not correlated with infant birthweight. It is possible that dietary modulations improve GDM pregnancy outcome, not only by improving glycaemic controls but also by affecting placental growth by altering the proportion of protein intake.