BreastSurgANZ members recommendations for adjuvant systemic treatment and patient compliance in Australian breast cancer patients.

BACKGROUND: We aimed to identify compliance with systemic treatment recommendations in early breast cancer (EBC) patients managed by Australian BreastSurgANZ members. METHODS: A retrospective analysis of patients diagnosed with EBC included in BreastSurgANZ prospective database from January 2002 to December 2016 was conducted. Data was available on patients with BC treated by over 350 surgeons across the six states and two territories of Australia. RESULTS: Over the 15 year period, 102 660 EBC episodes were recorded in 99 800 patients. As a group, the five key performance indicators (KPIs) set by the BreastSurgANZ relating to systemic treatment were achieved. Overall, patients were compliant with systemic treatment recommendations with 89.1% of patients receiving treatment in accordance with recommendations from their treating surgeon. The highest rate of non-compliance with systemic treatment was for endocrine therapy (11.9%). Of the 2368 patients who did not proceed with the recommended endocrine treatment, 1284 (54%) patients did so because of patient refusal. Failure to receive chemotherapy was associated with older age (aOR 1.02; p < 0.001), patients living in regional areas (aOR 1.23; p = 0.001) and those with node negative disease (aOR 0.97; p = 0.003). CONCLUSIONS: The majority of Australian patients with EBC are being recommended for adjuvant systemic therapy in accordance with BreastSurgANZ KPI's. Treatment compliance was very high. This finding emphasises the importance of prospective data collection and auditing of established KPIs by surgeons, in areas other than direct surgical outcomes. Further research into the reasons why patients refuse treatment is needed.

Psychosocial consequences in offspring of women with breast cancer.

OBJECTIVE: Breast cancer (BC) accounts for 24% of female cancers, with approximately one quarter of women likely to have offspring aged less than 25 years. Recent publications demonstrate negative psychosocial well-being in these offspring. We prospectively assessed for psychological distress and unmet needs in offspring of BC patients. METHODS: Eligible offspring aged 14 to 24 years were consented and completed the Kessler-10 Questionnaire and Offspring Cancer Needs Instrument. Demographic and BC details were obtained. RESULTS: Over a 7-month period, 120 offspring from 74 BC patients were included. Fifty-nine mothers had nonmetastatic BC (nMBC), and 27 had metastatic BC (MBC) with median time from diagnosis of 27.6 and 36.1 months, respectively. The prevalence of high/very high distress was 31%, with significantly higher scores reported by female offspring (P = .017). Unmet needs were reported by more than 50% of offspring with the majority of needs relating to information about their mother's cancer. Greater unmet needs were seen in female offspring and offspring with none or one sibling for several domains (practical assistance, time-out, dealing with feelings, and support from friends; P < .05). Greater unmet needs were seen in regard to feelings for MBC patients' offspring compared with nMBC but were similar for other unmet needs. CONCLUSIONS: Our study confirms high levels of psychological distress in offspring of BC patients, with female offspring reporting significantly higher emotional distress and unmet needs. More than 50% of respondents reported unmet needs in areas that can potentially be supported, including greater information provision, improving practical issues, and enabling sufficient recreational time.

Compliance with multidisciplinary team meeting management recommendations.

OBJECTIVES: The objective of this study was to evaluate patient compliance with management recommendations given by a breast cancer multidisciplinary team (MDT), assess for reasons for noncompliance, and perform an exploratory assessment on breast cancer outcomes in noncompliant patients. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data was undertaken for patients selected by their primary clinician to be discussed at the MDT of Breast Cancer Research Centre-WA in Perth between 1st March 2011 and the 28th February 2016. The primary objective was the rate of compliance with MDT management recommendations. Secondary objectives included factors associated with noncompliance, rate of clinical trial uptake, and impact of treatment noncompliance on breast cancer events in a subgroup of early breast cancer (EBC) patients. RESULTS AND CONCLUSION: A total of 2614 MDT management recommendations were made for 925 patients. Overall, 92% were compliant with all recommendations given. Clinical trial recruitment was successful in 84.1%. The reasons given for treatment noncompliance were fear of toxicity, choosing an alternative treatment, and treatment inconvenience. In a subset of 337 EBC patients, there was a significantly higher rate of contralateral breast cancer, distant recurrence, and breast cancer-specific death, P = .0016, in those who were noncompliant. Our study demonstrates a high rate of MDT treatment recommendation compliance and clinical trial recruitment. In a subgroup of EBC patients, noncompliance was associated with significantly worse outcomes. Attention to educating patients to minimize their fear of treatment toxicity and ensuring their understanding of evidence-based treatment may lead to lower rates of noncompliance.

A retrospective study investigating the rate of HER2 discordance between primary breast carcinoma and locoregional or metastatic disease.

BACKGROUND: Overall survival of HER2 positive metastatic breast cancer patients has been significantly improved with inclusion of trastuzumab to chemotherapy. Several studies have demonstrated discordant HER2 status in the primary and metastatic tumour. However, rates of discordance vary considerably in published reports. METHODS: Information collected prospectively was analysed for all patients seen from 1999 to 2009 with primary breast cancer and who had biopsy of a local or distant recurrence. Patients were included if adequate tissue was available from both paired samples. Recurrent samples included fine needle aspirations, core and excisional biopsies. HER2 status in all paired samples was assessed by in-situ hybridisation by a single pathologist in a national reference laboratory. This was compared with HER2 immunohistochemistry results provided in the course of routine diagnosis at regional laboratories. RESULTS: In total, 157 patients with recurrent (n = 137; 87.3%) or synchronous primary and metastatic (n = 20; 12.7%) breast cancer had biopsy of the metastatic site. The study population comprised of 116 patients with adequate tissue in both primary and metastasis. The concordance between HER2 status of the paired samples by local immunohistochemistry testing and central in-situ hybridization were 78% and 99%, respectively. Only one patient demonstrated HER2 discordance--primary lesion was positive whilst a metastatic site was negative. CONCLUSIONS: This single institution study demonstrated a low rate of HER2 discordance between primary and recurrent breast cancer as assessed by in-situ hybridisation. This contrasts to results reported by others, which may be explained by differences in study methodology, definition of recurrent disease samples and generally small numbers of patients assessed. Despite the current findings, the decision to obtain metastatic tissue for evaluation is influenced by other factors. These include disease-free interval, which may raise the possibility of a new malignancy and the accuracy of initial HER2 assessment of the primary tumour.

Preoperative taxane-based chemotherapy in a standardized protocol for locally advanced breast cancer.

AIMS: To assess the feasibility of a standardized multidisciplinary protocol for the management of locally advanced breast cancer (LABC). We also evaluated the accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) in predicting the extent of residual disease. METHODS: Patients with LABC were offered preoperative chemotherapy of docetaxel 75 mg/m(2) , doxorubicin 50 mg/m(2) , cyclophosphamide 500 mg/m(2) (TAC), every 21 days for six cycles, until progression or intolerable toxicity. MRI and PET were performed at baseline and six cycles. Patients underwent a mastectomy or complete local excision, followed by radiotherapy. Trastuzumab and endocrine treatment were recommended where appropriate. RESULTS: Between April 2005 and October 2006, 51 patients were included from three institutions, and 50 received TAC (90% commenced within 35 days of diagnosis), with 44 patients completing six cycles (88%). Pathological complete response was seen in 10 patients (19.6%); all had invasive ductal carcinoma. No patient with invasive lobular carcinoma achieved pathological complete response. MRI was the most accurate method of assessing the extent of residual cancer. In total, 45 (88%) patients underwent surgery within the protocol-specified time and 12 (23%) patients had breast conservation surgery. At a median follow-up of 41.3 months, there were three local recurrences. Ten patients (19.6%) developed distant metastases, resulting in an 80% actuarial disease-free survival. CONCLUSION: This regimen of TAC is effective and well-tolerated and is likely to result in improved outcomes since patients can receive optimal multimodality treatments.

The accuracy of intraoperative subareolar frozen section in nipple-sparing mastectomies.

BACKGROUND: Intraoperative subareolar frozen sections are used to assess the nipple areolar complex's suitability for preservation for patients selected for nipple-sparing mastectomy. We aim to investigate the accuracy and value of the frozen section compared to formal histopathologic results. METHODS: In our 5-year retrospective study, 52 candidates for nipple-sparing mastectomies had subareolar frozen sections analyzed intraoperatively for malignant or atypical duct changes. Women were considered for nipple-sparing mastectomy if their primary breast malignancy was greater than 3 cm from the nipple-areolar complex and not multifocal in nature. Frozen-section results were compared to the formal histopathologic results, allowing analysis of the sensitivity, specificity, and predictive value. Causes of false negatives (negative frozen-section findings, positive histopathology findings) were then examined. RESULTS: Of 52 frozen sections, 47 (90%) yielded negative results and 5 (10%) yielded positive results. Of the 47 negative results, 39 were true negatives while 8 were false negatives. Of the 5 positive results, all were true positives with no false positives. Therefore, the positive predictive value of subareolar frozen section is 100%, negative predictive value 83%, sensitivity 38%, and specificity 100%. Of the 8 false negatives, 4 (50%) were due to sampling errors, 3 (37.5%) were due to interpretation errors, and 1 (12.5%) was due to diathermy artifact. CONCLUSION: Intraoperative subareolar frozen section is a specific but nonsensitive test. It is useful in nipple-sparing mastectomy because in 10% of cases a positive result allows immediate nipple and areolar excision. Its low sensitivity and negative predictive value means that 15% of patients will need a subsequent nipple and areolar excision. Eighty-five percent of patients can, however, have a single-stage excision.

A novel ABCA1 nonsense mutation, R1270X, in Tangier disease associated with an unrecognised bleeding tendency.

The ATP binding cassette transporter A1 (ABCA1) is involved in the regulation of lipid trafficking and export of cholesterol from cells to high density lipoprotein (HDL). ABCA1 gene defects cause Tangier disease, an autosomal recessive disorder characterised by the absence of HDL-cholesterol in plasma, abnormal deposition of cholesteryl esters in the reticuloendothelial system, defective platelet dense and lysosomal granule release, and disordered cellular cholesterol efflux. We describe the case of a 62-year-old man with Tangier disease who presented with severe anaemia secondary to a spontaneous splenic haematoma. He underwent elective splenectomy without haemorrhage and his thrombocytopaenia resolved with a platelet count rising from 97 to 560 x 10(9)/L. Macroscopically, the resected spleen was enlarged with evidence of splenic haematoma. Histologic analysis of sections of spleen revealed lipid histiocytosis consistent with the diagnosis of Tangier disease. DNA sequence analysis revealed the subject to be a homozygote for a novel ABCA1 mutation c.4121C>T, which changes arginine 1270 to a stop codon (R1270X). In conclusion, we describe a case of Tangier disease in association with an unrecognised bleeding tendency, in a man homozygous for a novel ABCA1 gene mutation, R1270X.

Laparoscopic oophorectomy in the management of breast disease.

BACKGROUND: Oophorectomy is being increasingly carried out in the management of breast disease, as either adjuvant treatment for breast cancer or for prevention of ovarian and fallopian tube cancer in BRCA gene mutation carriers. The aims of this study were to determine the surgical outcome of laparoscopic oophorectomy when carried out by breast surgeons and whether laparoscopic oophorectomy can be safely carried out during the same anaesthesia as breast surgery. METHODS: Patients who had laparoscopic oophorectomy carried out by two breast surgeons were reviewed with regard to the indication, surgical outcome and concurrent procedures. Salpingectomy was also carried out when the indication was prevention. RESULTS: Seventy patients with breast disease had laparoscopic oophorectomy between January 2000 and June 2007. Forty-three patients had laparoscopic oophorectomy for adjuvant endocrine treatment of early breast cancer, 13 for prophylaxis, 7 for endocrine and prophylactic reasons and 7 for treatment of metastatic breast cancer. Sixteen patients had laparoscopic oophorectomy and breast surgery at the same time, without complication. Of note, four BRCA mutation carriers had prophylactic mastectomies, bilateral breast reconstruction and bilateral laparoscopic salpingo-oophorectomy. No patient required conversion to an open procedure, including 29 patients with previous abdominal surgery. There were no significant complications. Three patients had ovarian cancer or breast cancer detected in an ovary. CONCLUSION: Laparoscopic oophorectomy can be safely and efficiently carried out by breast surgeons with expertise in laparoscopic surgery. Previous abdominal surgery did not prevent a successful laparoscopic approach. Breast oncological and/or reconstructive surgery and laparoscopic oophorectomy can be reliably carried out as a combined procedure.

Multiple papillomas of the breast: is current management adequate?

Multiple papillomas (MP) are subject to debate in terms of their clinical and pathological significance and management. To date the ideal management is still not well established. The Royal Perth Hospital Multidisciplinary Breast Service has prospectively accrued clinical and pathological data on over 9000 patients since 1994. The database was interrogated and all pathology reports retrospectively reviewed. A total of 23 cases with the diagnosis of MP were retrieved from the database between 1994 and 2004. Of these 23 cases, 13 (56.5%) were diagnosed by core biopsy, nine (39.1%) on excision biopsy, and one (4.4%) on a mastectomy specimen. The average age of patients was 56.4 years (range 44-74 years). The average duration of follow up is 4.1 years (range 1-10 years). In our series a close association with malignancy was noted for MP, which was also associated with a spectrum of proliferative breast disease. Contemporary guidelines should be developed for this controversial condition. We recommend that all patients with MP, especially when associated with atypia, undergo wide excision of the lesion with clear margins of at least 10mm and that these patients be monitored closely with annual imaging.

Rates for mastectomy are lower in women attending a breast-screening programme.

BACKGROUND: Mammographic screening for breast cancer facilitates earlier recognition of lesions, thus potentially allowing for breast-conserving surgery. Few studies have compared the final surgical outcomes of women presenting through breast screening programmes with those presenting via other sources. Are breast cancer patients presenting through BreastScreen more likely to undergo breast-conserving surgery than those presenting from other sources? METHODS: Using the Royal Perth Hospital (RPH) Multidisciplinary Breast Service Database, the final surgical outcomes were reviewed for 723 women treated for breast cancer at RPH between January 2000 and August 2002. During this period, 397 patients were referred to the RPH Multidisciplinary Breast Clinic from BreastScreen WA, and 326 were referred from other sources. RESULTS: Of all patients undergoing surgery for breast cancer, 58% in the screen group and 36% in the non-screen group had breast-conserving surgery (P < 0.0001). When surgical outcomes for women in the BreastScreen target age range of 50-69 years were analysed, 59.5% in the screen group and 42.3% in the non-screen group had breast-conserving surgery (P < 0.001). Patient choice was second only to disease extent as a factor determining the outcome of mastectomy. In both cohorts, more than 40% of patients who underwent re-excisional surgery for positive margins, after initial breast-conserving surgery, had residual invasive or in situ disease present. CONCLUSIONS: At RPH, BreastScreen patients were more likely to undergo breast-conserving surgery than those who presented from other sources. A significant proportion of women with positive margins after initial breast-conserving surgery had residual in situ or invasive disease. Re-excision for positive margins was thus warranted.