Polly S. Y. Cheung

Diagnosis and treatment of functioning and nonfunctioning adrenocortical neoplasms including incidentalomas

The most important functional tumors of the adrenal cortex are those that secrete cortisol or aldosterone in excess. Biochemical testing when appropriately utilized can diagnose and differentiate the cause of Cushings syndrome, and when an adrenal adenoma is found, surgical excision is curative. The diagnosis and surgical treatment of primary aldosteronism are straightforward today, and localization of the usual small cortical tumor producing the syndrome can be achieved by CT and NP-59 scanning or selective venous assays. Adrenocortical carcinomas are relatively rare, are usually incurable when diagnosed, and are an important consideration in the incidentally discovered adrenal mass found by CT scanning.

Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer.

Background:The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC).Methods:We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2.Results:Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%).Conclusion:IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.

Multidisciplinary Approach to the Management of Breast Cancer in Hong Kong

Treatment of breast cancer has become more complex and sophisticated in recent years, and a multidisciplinary team approach to management is now recommended worldwide. The present study reviews the applicability of the multidisciplinary approach to the management of patients with breast cancer in a private hospital. Between September 2003 and April 2005, a total of 579 consecutive patients undergoing breast cancer surgery were studied. Patients receiving neoadjuvant chemotherapy or who had metastatic disease at presentation were excluded. Demographic and operative details, pathology, and recommended adjuvant therapy were discussed in the weekly multidisciplinary breast conference involving breast surgeons, pathologists, and radiation and medical oncologists. The mean age was 48.6 years. A self-discovered breast lump (80%) was the most common presentation, whereas screening mammography accounted for only 12.2%. The accuracy of preoperative mammography, ultrasonography, fine-needle aspiration cytology, and core biopsy were 66.5%, 80.7%, 89.4%, and 98.9%, respectively. Mastectomy was performed in 49.3% of patients, of whom 22.0% underwent immediate reconstruction. Eighty-five percent of patients underwent concomitant axillary surgery, comprising either sentinel node biopsy (49.9%), sentinel node biopsy followed by axillary dissection (38.7%), or axillary dissection alone (11.4%). The mean size of invasive tumors was 2.3 cm, and lymph node metastases were detected in 40% of patients; stage 0, I, II, and III disease was present in 14.2%, 34%, 44.5%, and 7.2% of patients, respectively. Adjuvant hormonal therapy, chemotherapy and radiotherapy were recommended in 62.4%, 51.2%, and 64.9% of patients, respectively. Breast cancer in Hong Kong most often presents as a breast lump discovered by self-examination. The role of screening mammogram has to be reevaluated. Multidisciplinary teamwork is essential for optimizing decision-making about adjuvant treatment interventions in such patients.

Evidence for a programing effect of early menarche on the rise of breast cancer incidence in Hong Kong

BACKGROUND Younger age at menarche and older age at first live birth are implicated as risk factors for breast cancer, but the extent to which these factors contribute to the sharply rising incidence of this disease in developing countries has received little study. METHODS We conducted a retrospective analysis of 702 consecutive breast cancer patients diagnosed at a single hospital in Hong Kong during 2003-2006. Comparisons were made between patients with different ages at cancer diagnosis (hence, belonging to different birth cohorts) and their respective ages at menarche and at first live birth. We then correlated these age-dependent differences with overall breast cancer incidence data from the Hong Kong Cancer Registry. RESULTS When patients diagnosed before age 40 are compared with those after 60, the age of menarche is lower in the former subgroup (12.7 vs. 14.2; p<10(-6)) while the age of first live birth is greater (28.2 vs. 25.5; p<0.01). However, registry data suggest that the progressive rise in breast cancer incidence has not affected those over 65, nor very young (20-39 years) patients. CONCLUSION Lifestyle variables that reduce age at menarche may contribute to the rising risk of breast cancer diagnosed after age 40 in Hong Kong, whereas earlier-onset cancers may be characterised by a distinct pathogenesis. Although retrospective, these data raise the possibility that cancer-preventive health interventions could gainfully target reversible risk factors favoring early menarche - such as formula infant feeding, high-fat diets, and lack of exercise - in children and adolescents living in developing countries such as China.

Benefit of Ultrasonography in the Detection of Clinically and Mammographically Occult Breast Cancer

ObjectiveThe purpose of this study was to evaluate the performance of high-resolution ultrasonography in the detection of clinically and mammographically occult breast cancer.Materials and methodsFrom September 2003 to November 2006, a total of 1485 patients were confirmed to have in situ or invasive breast cancer in Hong Kong Sanatorium and Hospital Breast Care Centre. All patients underwent mammography (MMG) and/ or sonography (USG) evaluation. Patients’ age and size of tumor detected by USG alone were compared with those detected by MMG.ResultsAltogether, 222 patients (17%) had positive imaging findings on USG only, among which 22 (13%) patients had nonpalpable tumors. Performing USG increased the cancer detection rate among clinically and mammographically occult breast lesions by 14.3%. The mean size of the tumors detected only by USG was 1.98 cm, which was not significantly different from the mean size of tumor detected by MMG (1.46) (p = 0.23). This remains true in the group of patients with nonpalpable tumors (1.36 vs. 1.46 cm, p = 0.88). The sensitivity of USG is 91%, which is significantly higher than that of MMG (78%) (p = 0.001). This remains true in patients age <40 or ≥40, tumor grading I toIII, and LVI +/− cases. However, MMG had higher sensitivity in the group of patients with nonpalpable tumors (73% vs. 62%, p = 0.01) and noninvasive cancers (72% vs. 69%, p = 0.01).ConclusionsThe use of high-resolution USG may lead to detection of a significant number of occult cancers that are no different in size from nonpalpable mammographically detected lesions.

Breast carcinoma in Chinese women: does age affect treatment choice and outcome?

OBJECTIVE Age is a known risk factor for breast cancer behaviour. We studied the relationship of age with clinical characteristics, tumour pathology, therapeutic options and outcome in an affluent Asian population. METHODS From 2003 to 2008, data on newly diagnosed breast carcinoma patients under the care of the multidisciplinary breast cancer team based at a private hospital in Hong Kong were collected prospectively. Patients were divided into three groups: age < 40 years (group I), 41-69 years (group II), and ≥ 70 years (group III). RESULTS There were 2,079 patients: 334 in group I, 1,538 in group II and 148 in group III. The clinical presentation and tumour stages were similar. Younger patients had higher tumour grading (p = 0.000) and more lymphovascular permeation (p = 0.011). For older patients, combination therapy was employed less frequently (p < 0.0005), and more radical resection with less reconstructive procedures were performed (p = 0.000). The 3-year disease-free survival was 97.8% and there was no difference between the three groups. CONCLUSION Although breast cancer in younger Chinese patients was more aggressive pathologically, the differences between clinical presentation, tumour staging and survival were similar. Treatment strategies should follow the clinical condition of the patient rather than age alone.

Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy

BackgroundAlthough invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity.MethodsThe clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed.ResultsTwo hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC tumors failed to demonstrate any such inverse relationship (p >0.6).ConclusionThese data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.

Women surgeons in Hong Kong

Objective:  To survey Hong Kong women surgeons current situation: their ability to balance career, personal and family life, and to look into some gender‐specific issues.

Ductal carcinoma in situ in Chinese women undergoing opportunistic breast cancer screening

Before the introduction of breast cancer screening in 1990, ductal carcinoma in situ (DCIS) was a rare disease, representing less than 2 per cent of all breast cancers in Chinese. With the availability of screening mammography, DCIS, which is believed to be the precursor of invasive breast cancers, is diagnosed with increasing frequency. In the present study, we evaluated the impact of breast cancer screening by comparing the clinicopathological differences between screen‐detected and symptomatic DCIS in the largest cohort of Chinese women.

Panmucositis and chemosensitisation associated with betel quid chewing during dose-dense adjuvant breast cancer chemotherapy.

Purpose: The severity of chemotherapy-induced oral mucositis has previously been reported to be greater in patients who chew betel quid (areca), an addictive habit shared by hundreds of millions of individuals worldwide. Here, we report a case of fulminant panmucositis complicating dose-dense adjuvant breast cancer treatment in a betel-chewing patient without evidence of other risk factors. Methods: Grade IV mucositis was triggered by the initial use of standard-dose anthracycline chemotherapy, and involved not only the mouth but also the genital and anal mucosa, as well as other severe non-mucosal toxicities. Results: Despite subsequent treatment with dose-reduced CMF and docetaxel regimens—which are seldom associated with mucosal toxicity at these dose intensities in the absence of neutropenia—high-grade oral mucositis continued to complicate the therapeutic course. Conclusion: These observations suggest that the potentiation of chemotherapy-induced mucositis by quid chewing may not be mediated solely by local effects on the oral epithelium, but also involves the systemic absorption of toxic chemosensitising molecules.