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Aims: Multidisciplinary meetings (MDMs) play a crucial role in decision‐making in breast cancer patient care. This study aimed to firstly assess the impact of breast cancer MDMs in decision‐making for breast cancer patients and secondly to determine the concordance between MDM recommendations and implementation of clinical practice. Methods: Patient cases to be presented at the weekly breast cancer MDMs were identified and prospectively enrolled. Management plans were predicted by the treating surgeon with the pre‐MDM management plans then compared to MDM recommendations. Changes in decision‐making were assessed in the following domains: further surgery, systemic therapy (endocrine, chemotherapy or targeted), radiotherapy, enrolment in a clinical trial, further investigations, and referral to other specialists or services. Patient records were subsequently reviewed at 3 months post‐MDM to assess the rate of implementation of MDM recommendations and any reasons for discordance. Results: Out of 50 cases, 66% (CI 53–79%; p <.005) experienced a change in management plan as a result of MDM discussion, with a total of 66 episodes of recorded change per decision‐making domain affecting the following: further surgery (7.6%), endocrine therapy (4.5%), chemotherapy (19.7%), targeted therapy (4.5%), radiotherapy (18.2%), enrolment for a clinical trial (12.1%), additional investigations (22.7%), and further referrals (10.6%). MDM recommendations were implemented in 83.7% of cases. Conclusion: The breast cancer MDMs were found to substantially impact on the management plans for breast cancer patients, with 83.7% of MDM recommendations being implemented into clinical practice. This study reinforces the importance of MDMs in the management of these patients, as well as highlighting the need for further investigating and addressing the potential barriers to the implementation of MDM recommendations. [ABSTRACT FROM AUTHOR]

Cyclin‐dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been approved for breast cancer (BC) treatment. Several trials suggested that arthralgia was reduced in patients treated with ET plus CDK4/6i compared with that in those with ET‐alone. We aimed to compare arthralgia rates in BC patients treated with/without CDK4/6i. We reviewed randomized controlled phase II/III trials investigating CDK4/6i with ET in hormone receptor‐positive and epidermal growth factor 2‐negative BC. Publications were retrieved from PubMed from January 2014 to April 2021. We compared arthralgia rates between patients who were administered ET plus CDK4/6i (CDK4/6i group) and those treated with ET‐alone (control group). We reviewed 12 trials that reported data on adverse effects for arthralgia. These trials included 17,440 patients (9255 in the CDK4/6i group and 8185 in the control group). The arthralgia rate in the CDK4/6i group was significantly lower than that in the control group (27.6% vs. 34.8%, p <.001), especially in early BC (28.8% vs. 37.3%, p <.001). These suggested that the arthralgia rate in patients treated with ET plus CDK4/6i was lower than that in patients treated with ET‐alone and that CDK4/6i may decrease the arthralgia rate in BC patients treated with ET, especially in early BC. [ABSTRACT FROM AUTHOR]

Aim: The majority of women diagnosed with early breast cancer have hormone‐receptor positive (HR+)/HER2‐negative disease. Adjuvant endocrine therapy provides substantial risk reduction benefits in virtually all patients. The role of adjuvant chemotherapy in certain subsets of patients is equivocal. This paper sought to evaluate the role of the IHC4+C score to aid this clinical decision in addition to providing an overview of the current molecular and non‐ molecular tools available in the adjuvant setting. Methods: This prospective study included 53 post‐operative HR+/HER2‐ negative early breast cancer patients selected from the multidiscipliniary team meeting between August 2017 and January 2020. IHC4+C testing was requested by clinicians for patients in whom the availability of the score may have impacted adjuvant decision‐making. Adjuvant treatment decisions were recorded at three time points (prior and post IHC4+C scoring as well as the patient's final decision). The primary goal was the proportion of patients who were spared chemotherapy following the availability of IHC4+C scores to impact on clinicians' recommendations for adjuvant systemic therapy. Results: A total of 34 patients (64%) were initially recommended to undergo chemotherapy or to consider chemotherapy. With the availability of the IHC4+C score, only 17 patients (32%) underwent chemotherapy, demonstrating a substantial reduction in the frequency of chemotherapy prescribing. Conclusion: This study demonstrates that when utilized appropriately in a multidisciplinary setting, the IHC4+C algorithm is an alternative, reproducible and affordable tool with a proven capacity to stratify risk and to spare a large proportion of patients from undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Patients presenting with hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2–) metastatic breast cancer (MBC) are usually treated with endocrine therapy (ET), except if there is a concern about endocrine resistance or a need to achieve rapid disease control due to visceral crisis. The combination of CDK4/6 inhibitor + ET has now replaced single‐agent ET as the standard first‐line treatment; and it can also be considered a standard option in the second‐line setting. This review briefly summarizes recently reported efficacy findings from the key phase III clinical trials of CDK4/6 inhibitor + ET in patients with HR+/HER2– MBC, including evidence that adding a CDK4/6 inhibitor to ET improves overall survival and does so without reducing patients' quality of life. There is still much to learn regarding the use of CDK4/6 inhibitors and how they may be optimally integrated into clinical practice. In particular, there is a need for specific biomarkers that help predict the likelihood of response or resistance to CDK4/6 inhibitor therapy; and for data to guide treatment decisions when a patient's disease progresses on a CDK4/6 inhibitor. [ABSTRACT FROM AUTHOR]

Aim: There is no consensus regarding the association between hormone replacement therapy (HRT) and risk of meningioma so far. We conducted the first study among Chinese female patients to investigate the influence of HRT use on the risk of meningioma. Methods: We retrospectively collected records of diagnosis of meningioma for women aged 50 years and above during 2011–2016 and dispense of HRT prior to meningioma diagnosis in three tertiary hospitals in China. Meningioma cases were matched with controls at a ratio of 1:2 by using nearest neighbor propensity scores matching in order to balance the baseline characteristics between groups, which generated a total of 629 cases with 1258 controls. Results: We observed prior use of HRT associated with increased risk of meningioma (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0–1.4) and the association was more prominent among women having multiple HRT dispenses and longer term exposure (OR, 1.3; 95% CI, 1.1–1.6), among those with combination therapy of estrogens and progestogens (OR, 1.3; 95% CI, 1.1–1.7) than monotherapy, and among progestogen users than estrogen users as for monotherapy. Furthermore, vaginal, subcutaneous implant seems to be associated with a higher risk of meningioma compared with oral administration although no significance had been reached. Conclusion: This case–control study provides evidence that hormone use for an HRT purpose might constitute the development and growth of meningioma as an independent risk factor, especially for combination therapy and/or long‐term users, which supports that meningioma might be a hormone‐sensitive tumor. [ABSTRACT FROM AUTHOR]

Objectives: Industry‐supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24–40% of hormone receptor+/HER2− patients. ODX is not reimbursed by third‐party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self‐funded ODX on TRs. Methods: Data collected included demographics, tumor characteristics, indication for ODX and pre‐ and post‐recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought. Results: Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18‐31) in 36% and high (≥32) in 9%. Thirty‐eight percent of patients had TR change post‐ODX. Sixty‐five percent of patients recommended CT pre‐ODX changed to hormone therapy alone (HT)—more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre‐ODX TR for HT added CT—more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%. Conclusion: Patient‐funded ODX changed TRs in 38% of patients, de‐escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry‐funded study suggesting that physicians can identify situations where the assay may influence decisions. [ABSTRACT FROM AUTHOR]

The treatment of metastatic hormone‐sensitive prostate cancer (mHSPC) has been rapidly evolving. In the past, the use of chemotherapy was reserved for metastatic prostate cancer patients who developed castration resistance. Subsequently, there were three well‐designed randomized controlled trials investigating the use of chemotherapy together with androgen deprivation therapy as the first‐line treatment for metastatic hormone‐sensitive prostate cancer. The GETUG‐AFU 15 study was a negative trial, but the subsequent CHAARTED and STAMPEDE studies demonstrated magnificent survival benefit in the mHSPC setting. Since then, the use of chemohormonal therapy has become accepted and popularized worldwide. However, these results were largely based on Caucasians. Because of the genetic and physiological differences between different ethnicities, there has been concern over whether these results could be readily translated to the Asian population. Would Asians in general have a different tolerability towards chemohormonal therapy? Would prostate cancer in the Asian population have a different biological response towards chemohormonal therapy? In this review paper, we will present the available data regarding the use of chemohormonal therapy for mHSPC and discuss their implications from an Asian perspective. [ABSTRACT FROM AUTHOR]

Abstract: Resistance to endocrine therapy is a significant therapeutic challenge in the treatment of women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2–) advanced breast cancer. Cyclin‐dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy have been shown to improve progression free survival, overall response rate and clinical benefit rate in women with HR+ HER2– metastatic breast cancer compared with endocrine therapy alone. This review examines the clinical evidence to support the use of CDK4/6 inhibitors in first and second line settings. Practical guidance is provided for the use of CDK4/6 inhibitors, including tolerability data, monitoring requirements and management of key toxicities for each of the available agents. [ABSTRACT FROM AUTHOR]

Abstract: Cyclin‐dependent kinase (CDK4/6) inhibitors in combination with endocrine therapy are currently the optimal first line treatment for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) non‐amplified metastatic breast cancer (MBC). However, not all patients benefit from this treatment and all patients will inevitably progress. Identifying therapeutic strategies in this setting is therefore of immediate clinical importance. We present an overview of the mechanisms of resistance to CDK4/6 inhibitors and review potential biomarkers that may guide therapy selection. We also discuss the use of CDK4/6 inhibitors in the context of non‐HR‐positive/HER2‐non‐amplified breast cancer and in combination with therapies other than endocrine therapy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: A substantial survival benefit with chemohormonal therapy has been proven by the CHAARTED and STAMPEDE studies, and this clinical approach has emerged as the standard of care for patients with metastatic hormone‐naïve prostate cancer (mHSPC). However, because its clinical efficacy and tolerability in Asian patients remains uncertain, this study aims to evaluate preliminary results of its use in Hong Kong. Methods: The clinical records of mHSPC patients treated with chemohormonal therapy from all six public oncology centers in Hong Kong between January 2015 and July 2016 were reviewed. Time to castration‐resistant prostate cancer (CRPC), treatment‐related complications, prostate‐specific antigen (PSA) response and the time to PSA nadir were assessed. Results: A total of 32 patients (median age, 66 years) were treated with chemohormonal therapy in the review period. After median follow‐up time of 11.4 months, the median time to CRPC and time to PSA nadir were 19.5 months and 7 months, respectively. PSA response (>50% drop in PSA level from baseline) was achieved in all patients and the median maximal PSA response was 99.6%. The rates of grade 3 or 4 febrile neutropenia, neutropenia and anemia were 12.5%, 40.6% and 3.1%, respectively. Conclusion: Early efficacy with chemohormonal therapy in Asian mHSPC patients was comparable to the pivotal study and biochemical response is promising. The high frequency of hematologic toxicities in Asian patients highlights the importance of proper patient selection and pre‐emptive use of granulocyte colony‐stimulating factor. [ABSTRACT FROM AUTHOR]

Aims To determine the frequency, timing and patterns of endocrine therapy switching in Australian practice for postmenopausal women with primary breast cancer. Methods We identified postmenopausal women in a population-based cohort commencing endocrine therapy for invasive primary breast cancer between December 2005 and December 2008 ( n = 645). Individual-level administrative health records and self-report data were used to determine women's demographic and clinical characteristics, including preexisting and newly-treated comorbidities, and switches in endocrine therapy. Time to therapy switching was calculated. Chi-square tests compared the characteristics of women who did and did not switch, and those switching within 2 years or after 2 years of commencing therapy. Results Twenty-eight percent of women switched from their initial endocrine therapy, most commonly from tamoxifen to anastrozole, or the converse. A small number of anastrozole-to-exemestane and letrozole-to-exemestane switches were observed ( n = 19). Most women (>80%) who switched therapies did not have newly-treated comorbidities. Few women (<5%) switched before completing 2 years of therapy, but these women were significantly more likely to have preexisting antidepressant use than women switching later (43% vs 23%, P = 0.048) and remained on the subsequent therapy for less time (6 months vs 2.7 years, P < 0.001). Conclusions Approximately one-quarter of postmenopausal women with primary breast cancer switched endocrine therapies. The findings suggest that the majority of switching in Australian practice was planned; occurring after 2-3 years of, not precipitated by comorbidity, and in a sequence supported by trial evidence. Early switching, however, was associated with preexisting depression and appeared to be a marker of poor persistence. [ABSTRACT FROM AUTHOR]

Primary adenoid cystic carcinoma of the lung is a rare subtype of lung cancer with a prolonged natural history but is difficult to completely resect surgically due to its proximal location. Hence radiotherapy plays a role for local control of these cancers. The role of systemic therapies in the treatment of adenoid cystic carcinoma of the lung remains unclear. Isolated case reports have previously described the treatment of primary adenoid cystic carcinoma of the lung with tamoxifen, resulting in partial control. We report the first case of primary adenoid cystic carcinoma of the lung treated with primary chemoradiotherapy due to unresectable location of the tumor, and disease stabilization with symptomatic response to tamoxifen following tumor recurrence. There is a need for further studies to investigate the role of anti-hormonal therapies in the treatment of adenoid cystic carcinoma of the lung. [ABSTRACT FROM AUTHOR]

Endocrine therapy for the treatment of hormone receptor positive, HER2 negative, metastatic breast cancer is continually evolving. We systematically reviewed phase 2 and 3 randomized controlled trials (RCTs) of agents used in this setting to assess the effectiveness and safety of these agents for postmenopausal women. Across the 32 studies in more than 10 000 patients, the greatest improvement in progression-free survival (PFS) was seen with the addition of a cyclin-dependent kinase (CDK)4/6 inhibitor to standard endocrine therapy. Treatment with a mammalian target of rapamycin (mTOR) inhibitor, phosphoinositol-3-kinase (Pi3K) inhibitor, vascular endothelial growth factor (VEGF) inhibitor and with a selective estrogen receptor degrader (SERD) also showed benefit in PFS for selected trials. Overall survival (OS) improved with the use of mTOR inhibitors and a SERD; however, studies were not powered for an OS endpoint. Encouraging results from early studies of histone deacetylase (HDAC) and B-cell lymphoma (BCL2) inhibitors are yet to be confirmed in phase III clinical trials. Study discontinuation rates and toxicity-related deaths were highest with VEGF inhibitors in combination with endocrine therapy, limiting their use in hormone receptor positive breast cancer. CDK4/6 inhibitors and mTOR inhibitors appeared to have activity in both first and second line settings, but required additional monitoring for common toxicities. The activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors was limited to the first-line setting and treatment discontinuation rates were higher than with mTOR inhibitors and SERDs. Overall, PFS benefit appears to be greatest when agents acting on CDK4/6, mTOR and Pi3K pathways, and SERDs are added to standard endocrine therapy. If these early results persist in further studies, these data are likely to change the way we treat hormone receptor positive, HER2 negative metastatic breast cancer. In the follow-up article to this review, we will consider the potential future treatment options for these patients. [ABSTRACT FROM AUTHOR]

Endocrine therapy is an established and effective treatment strategy for hormone receptor positive metastatic breast cancer. The clinical utility of endocrine therapy is lost over time due to evolving changes in tumor biology and the development of endocrine resistance. Many agents targeting the intracellular signaling pathways associated with endocrine resistance are in development. Encouraging early results have been seen for agents which directly target the estrogen receptor (ER), inhibitors of co-signaling pathways, inhibitors of ER chaperones, ER antagonists able to inhibit mutated or otherwise activated ERs, and modulators of histone acetylation restoring synthesis of ER signaling components. Following our systematic review of treatments with established benefits in this supplement, we review some of the more promising new strategies for overcoming endocrine resistance, looking at the impact on disease control and quality of life for women with hormone receptor positive, HER2 negative breast cancer. We also examine the biomarkers that may guide selection of the best therapy for the individual. [ABSTRACT FROM AUTHOR]

Aim We aimed to systematically review and summarize data from the available clinical trials that examined the treatment of HER2-positive metastatic breast cancer. Methods We reviewed phase 2 and 3 studies in which an anti- HER2 agent was used in one or both arms of the study. While formal meta-analysis was not possible for such a heterogeneous group of trials, resulting forest plots outline some generalizable findings. Results There is strong evidence that the addition of an anti- HER2 agent to standard chemo- or endocrine therapy improves clinically relevant measurable outcomes. There is also consistent evidence that initial treatment with trastuzumab alone (and subsequent use of a cytotoxic) is inferior to the initial combination of trastuzumab plus chemotherapy, and that either T-DM1 or dual anti- HER2 agents are superior to single anti- HER2 agent regimens. There is no strong evidence that the use of more than one cytotoxic agent together with an anti- HER2 agent confers any benefit over a single cytotoxic, anti- HER2 combination. Conclusion This review provides a strong evidence base for current clinical practice with a discussion of treatment in the Australian setting. [ABSTRACT FROM AUTHOR]

Aim To assess the performance of a proxy for estrogen receptor ( ER) status in breast cancer patients using dispensing data. Methods We derived our proxy using 167 patients. ER+ patients had evidence of at least one dispensing record for hormone therapy during the lookback period, irrespective of diagnosis date and ER- had no dispensing records for hormone therapy during the period. We validated the proxy against our gold standard, ER status from pathology reports or medical records. We assessed the proxy's performance using three lookback periods: 4.5 years, 2 years, 1 year. Results More than half of our cohort (62%) were >50 years, 54% had stage III/ IV breast cancer at recruitment, (46%) were diagnosed with breast cancer in 2009 and 23% were diagnosed before 2006. Sensitivity and specificity were high for the 4.5 year lookback period (93%, 95% CI: 86-96%; and 95%: 83-99%), respectively) and remained high for the 2-year lookback period (91%: 84-95%; and 95%: 83-99%). Sensitivity decreased (83%: 75.2-89%) but specificity remained high (95%: 83-99%) using the 1-year lookback period and the period is long enough to allow sufficient time for hormone therapy to be dispensed. Conclusion Our proxy accurately infers ER status in studies of breast cancer treatment based on secondary health data. The proxy is most robust with a minimum lookback period of 2 years. [ABSTRACT FROM AUTHOR]

Despite a survival benefit in the first-line treatment of castrate-resistant prostate cancer (CRPC) with docetaxel, the prognosis remains limited. There are increasing options available for patients with CRPC in the second-line setting, but there is currently little consensus regarding the optimal treatment. There have been numerous phase II and retrospective studies examining second-line options in CRPC, including retreatment with docetaxel, mitoxantrone, cyclophosphamide and carboplatin, which can be associated with meaningful responses in a significant minority of patients. In 2010 three randomized trials were published or presented which demonstrated a survival benefit in the second-line setting. These included cabazitaxel compared with mitoxantrone, sipuleucel-T (immunotherapy) and abiraterone acetate versus placebo. Ongoing research in the second-line setting of CRPC to optimize treatment options, with the objectives of survival prolongation, improvement in quality of life and pain management, is still needed. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include the genetic risk assessment for persons who are at risk of familial breast cancer, a comparison of a single agent against combination chemotherapy for metastatic breast cancer, and a comparison of surgery versus primary endocrine therapy for elderly women with operable primary breast cancer.

The aim was to examine patterns of practice in the adjuvant systemic treatment of early breast cancer in order to determine consistency of practice, areas of controversy and whether practice is evidence based.A survey was sent to all Medical Oncologists listed with the Medical Oncology Group of Australia (n = 291) in September 2003. Demographics and information on the use of aids to assist clinical decision making were obtained. Seven short case scenarios were provided and oncologists asked what systemic treatment they would recommend (outside a clinical trial), for a woman with no significant comorbidities.There were 106 replies (36%); 81 (28%) treating women with early breast cancer. Demographic data was available for 80/81 respondents and treatment details on all 81. The majority treated more than 20 patients/year; 52/80 (65%). Respondents represented a reasonable cross section of Australian oncologists with approximately 25% responding from most states and higher rates from several smaller states. Forty-nine (61%) used prognostic tables or aids. The responses received suggest that practice patterns in Australia are consistent with current evidence and in general comply with international guidelines. There was a tendency to treat patients at high risk with anthracyclines and with higher doses and longer courses. Younger patients were treated more aggressively. A greater variety of regimens were recommended for very high risk patients suggesting a lack of consensus. Of concern, a small proportion recommended tamoxifen for estrogen receptor-negative disease and others did not recommend its use for estrogen receptor-positive disease. [ABSTRACT FROM AUTHOR]

The article discusses the highlights of various research on prostate cancer. A study found that the use of five-alpha-reductase inhibitors may increase the risk of high-grade prostate cancer in men undergoing screening. Another study suggests an improvement in overall survival, pain relief and quality of life with chemotherapy for hormone-refractory prostate cancer. One study examined the role of hormones in combination with surgery and radiotherapy for prostate cancer.