Pathological and clinical outcomes following neoadjuvant dual HER2 therapy for early-stage breast cancer: An Australian institutional real-world experience.

AIM: There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non-metastatic HER2-positive breast cancer, which may be used in combination with conventional chemotherapy to optimise pathological responses at surgery. However, these therapies, particularly the chemotherapeutic components, may portend significant and long-lasting toxicity. Hence, de-escalation of treatment intensity has been an area of interest and was evaluated in the phase II NeoSphere study. Herein, we report the real-world pathological and survival outcomes from neoadjuvant taxane and dual HER2 blockade recorded at our centre. METHODS: This was a retrospective cohort study of patients receiving neoadjuvant pertuzumab, trastuzumab and taxane chemotherapy for non-metastatic HER2-positive breast cancer at a single centre in Sydney, Australia. We collected data pertaining to baseline demographic characteristics, pathological response rates, post-surgical prescribing patterns and also undertook survival analyses for invasive disease-free survival (iDFS) as well as exploratory analyses for correlations between pre-specified clinicopathologic factors and pathological response at surgery. RESULTS: Our population was largely similar at baseline to the NeoSphere study. 71 patients were included in the final analysis. 61% achieved a pathological complete response (pCR). Three patients received conventional chemotherapy in the adjuvant setting. 92% of included patients were alive and disease-free at 3 years of follow-up. Only 3 events of recurrence or death were recorded at a median follow-up of 32 months. No significant difference in iDFS was noted between patients achieving pCR and those with residual disease at surgery. CONCLUSION: This study demonstrates that de-escalated adjuvant treatment for HER2-positive early breast cancer achieved favourable pathological and long-term outcomes comparable to large trials, some utilising more intensive chemotherapeutic components.

Comparison of breast cancer HER-2 receptor testing with immunohistochemistry and in situ hybridization.

PURPOSE: Human epidermal growth factor receptor-2 (HER2) status can be tested with immunohistochemistry (IHC) and in situ hybridization (ISH). The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guidelines suggest initial HER2 testing using IHC and further testing IHC equivocal cases with ISH. However, many institutions perform both IHC and ISH on the same specimen. This study aims to analyze the concordance between HER2 IHC and ISH in order to evaluate the benefit of repeating HER2 testing on the same breast cancer specimens. METHOD: Patients diagnosed with invasive breast cancer through BreastScreen NSW Sydney West program between January 2018 and December 2020 were identified and their HER2 IHC and HER2 ISH results on core needle biopsy (CNB) and surgical excisions (SE) were retrospectively collected. Specimens with both IHC and ISH results were then analyzed for agreement and concordance using unweighted kappa values. Equivocal IHC (2+) cases were excluded from concordance analysis. RESULTS: Overall, there were 240 invasive breast cancer specimens (CNB and SE) with both IHC and ISH recorded. Concordance between HER2 IHC and ISH was 100% (95% CI: 96.2-100%; κ = 1.00 (P < 0.001)). Of the IHC equivocal cases (n = 146), 94.5% were ISH negative. CONCLUSION: There was perfect positive concordance and agreement between non-equivocal IHC and ISH results. This reinforces that IHC alone can be utilized reliably for testing HER2 status of non-equivocal cases consistent with the 2018 ASCO/CAP guidelines.

The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.

Introduction: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score. Methods: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11-25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%). Conclusion: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.

Concordance between core needle biopsy and surgical excision for breast cancer tumor grade and biomarkers.

PURPOSE: Histopathological biomarkers guide breast cancer management. Testing histopathological biomarkers on both core needle biopsy (CNB) and surgical excision (SE) in patients who are treated with upfront surgery is unnecessary and costly if there is high concordance between the two. This study investigated the concordance between CNB and SE for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), tumor grade and Ki-67. METHODS: Histopathological biomarker information were retrospectively collected from preoperative CNB and SE on patients diagnosed with breast cancer through the BreastScreen Sydney West program over a four-year period between January 2017 and December 2020. Data were then analyzed to calculate percentage of agreement and concordance using kappa values for ER, PR, HER2, tumor grade and Ki-67. RESULTS: A total of 504 cases of invasive breast cancers were analyzed. There was substantial level of concordance for ER 96.7% (κ = 0.687) and PR 93.2% (κ = 0.69). Concordance for HER2 negative (IHC 0, IHC 1 +) or positive (IHC 3 +) tumor on CNB was 100% (κ = 1.00). Grade and Ki-67 showed moderate level of concordance, 72.6% (κ = 0.545) and 70.5% (κ = 0.453), respectively. CONCLUSION: ER, PR and HER2 show high level of concordance. CNB is reliable in determining histopathological biomarkers for ER, PR positive and HER2 positive or negative tumors indicating that retesting these on SE may not be necessary.

Occult metastatic thyroid cancer diagnosed during breast cancer axillary sentinel node biopsy.

SUMMARY: In most developed countries, breast carcinoma is the most common malignancy in women and while thyroid cancer is less common, its incidence is almost three to five times greater in women than in men. Since 1966, studies have demonstrated an association between thyroid and breast cancer and despite these studies, the mechanism/s by which they are related, remains unclear. We present a case of a 56-year-old lady who initially presented in 2014 with a screen detected left breast carcinoma but was subsequently found to have occult metastatic thyroid cancer to the axilla, diagnosed from a sentinel node biopsy from the primary breast procedure. The patient underwent a left mastectomy, left axillary dissection and total thyroidectomy followed by three courses of radioactive iodine ablation. Despite this, her thyroglobulin level continued to increase, which was secondary to a metastatic thyroid cancer parasternal metastasis. Breast and thyroid cancer presents metachronously or synchronously more often than by chance. With improving mortality in primary cancers, such as breast and differentiated thyroid cancer, it is likely that as clinicians, we will continue to encounter this association in practice. LEARNING POINTS: There has been a long-standing observation of an association between breast and thyroid cancer although the exact mechanism of this association remains unclear. Our patient presented with thyroid cancer with an incidental diagnosis from a sentinel node biopsy during her primary breast operation for breast cancer and was also found to have a parasternal distant bony metastasis. Thyroid axillary metastases are generally rare. The interesting nature in which this patient's metastatic thyroid carcinoma behaved more like a breast carcinoma highlights a correlation between these two cancers. With improving mortality in these primary cancers, clinicians are likely to encounter this association in clinical practice. Systemic therapy for metastatic breast and thyroid cancers differ and therefore a clear diagnosis of metastasis is crucial.

Pathological outcomes of HER2-positive non-metastatic breast cancer patients treated with neoadjuvant dual anti-HER2 therapy and taxane: An Australian experience.

AIMS: Internationally, there has recently been growing interest in the use of neoadjuvant pertuzumab and trastuzumab in patients with non-metastatic HER-2 positive breast cancer following the NEOSPHERE trial in 2012. However, pertuzumab is currently not funded by the Pharmaceutical Benefits Scheme (PBS) in Australia for use in this setting. The authors sought to assess the clinical and pathological response rates at the time of surgery in patients who received neoadjuvant dual anti-HER2 and taxane therapy in a multidisciplinary breast cancer unit. METHODS: A retrospective case series of all patients treated with the neoadjuvant therapy, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. RESULTS: Nineteen patients were included in the study. Sixty-eight percent of all patients achieved pCR, of which 54% further demonstrated no residual ductal carcinoma in situ. Eight patients (42%) had N1 disease pretreatment, of these 88% demonstrated total pCR in the axilla and the breast. Most adverse effects to treatment were manageable grade 1-2 side effects. CONCLUSION: This is the first reported Australian experience using neoadjuvant dual anti-HER2 and taxane therapy for HER-2 positive nonmetastatic breast cancer. The authors have demonstrated favorable pCR rates for invasive disease compared to the NEOSPHERE trial (68% vs 46%), with reasonable patient tolerability. Larger collaborative data sets are required to fully evaluate correlation of pCR with survival outcomes, and cost-effectiveness. National funding models need to be considered.

Effect of the American College of Surgeons Oncology Group Z0011 trial on axillary management in breast cancer patients in the Australian setting.

The American College of Surgeons Oncology Group Z0011 Trial demonstrated that early breast cancer patients with positive axillary sentinel lymph nodes treated with breast-conserving surgery and breast radiotherapy had no additional oncologic benefit of proceeding to an axillary lymph node dissection (ALND). The extent to which practice has changed in Australia remains unclear. The aim of this study was to investigate the effect of the Z0011 trial on the management of positive axillary sentinel nodes at an Australian institutional level. We reviewed all breast cancer cases treated at the Sydney Adventist Hospital over a 10-year period from 1 January 2008 to 31 December 2017. Patients who fulfilled the Z0011 trial criteria were selected. These patients were divided into two groups according to the year of surgery, before and after 1 January 2011 when the Z0011 study was published. Clinicopathologic data and axillary surgical management were compared. Of the 237 patients fulfilling the Z0011 trial criteria, there were 73 patients before and 158 patients after 1 January 2011. In the earlier group the rate of proceeding to an ALND following a positive sentinel node was 78.1% compared to 43.7% in the latter group (P < 0.0001). There was a significant decline in the rate of ALND over this 10-year period (r = -0.79, P = 0.006). The Z0011 trial has influenced the surgical management of the axilla leading to a significant reduction in the rate of an ALND in patients fulfilling the Z0011 trial criteria at our institution.

Axillary reverse mapping in patients with breast cancer: Is it oncologically safe?

BACKGROUND: Axillary reverse mapping (ARM) is a technique used to identify the lymphatics draining the arm. The aim of this study was to examine the prevalence and predictors of ARM node metastases in breast cancer patients undergoing an axillary lymph node dissection (ALND). METHODS: A total of 87 patients were enrolled in this study. Patent V Blue dye was injected in the upper arm for ARM node localization. All patients had an ALND with the identified ARM node removed and sent separately for histologic analysis. RESULTS: Of 67 (77%) patients in whom an ARM node was identified, 49 (73%) were negative and 18 (27%) were positive for metastases on final histopathology. Positive ARM node status was significantly associated with advanced axillary disease, and larger primary cancers. Patients requiring a completion ALND due to a positive sentinel lymph node biopsy (SLNB) with non-suspicious ARM nodes during surgery did not have ARM node metastases. CONCLUSIONS: There is a high risk of ARM node involvement, approximately a quarter, in patients with preoperatively known lymph node metastases from breast cancer. However, it may be safe to preserve a clinically non-suspicious ARM node in patients with a positive SLNB who require a completion ALND. J. Surg. Oncol. 2016;113:726-731. © 2016 Wiley Periodicals, Inc.

Relevance of the American College of Surgeons Oncology Group Z0011 Trial to breast cancer in the Australian setting.

BACKGROUND: Conventional wisdom suggests that a patient with a positive sentinel node requires a completion axillary clearance to obtain full staging and durable regional control. However, this dictum has been challenged by the recent American College of Surgeons Oncology Group Z0011 Trial demonstrating that women with node-positive breast cancer who underwent sentinel node biopsy only, and were treated with breast conserving surgery and radiation, had equivalent locoregional recurrence and survival rates to those who had a completion axillary clearance. The aim of our study was to determine what the clinical impact of the Z0011 findings might be if patients were managed according to the Z0011 criteria in an Australian teaching hospital setting. METHODS: We performed a retrospective review, using prospectively collected data, of all female patients with breast cancer assessed at the Westmead Breast Cancer Institute in 2010 and identified the subgroup who would potentially have fulfilled all Z0011 criteria. The characteristics and management of this group were compared with node-positive and to mastectomy patient subgroups. RESULTS: A total of 280 patients with invasive breast cancer were identified. Twenty-six patients satisfied all Z0011 criteria, representing 9.3% of all patients and 21.5% of node-positive patients. Twenty-two (84.6%) patients had a subsequent axillary clearance, with six (27.3%) having additional positive nodes. CONCLUSIONS: The Z0011 study is relevant to 9.3% of all breast cancer patients and 21.5% of node-positive breast cancer patients treated in a major Australian teaching hospital.

Preoperative factors prolonging the length of stay in elective colorectal surgery.

BACKGROUND: In elective colorectal resections, the patient's preoperative social situation may play a significant role in delaying their discharge from hospital. The aim of this study was to identify which preoperative factors are associated with non-medical reasons for a delay in discharge and prolonged length of stay (LOS) in hospital after elective colorectal resections. METHODS: A retrospective review of prospectively collected data was performed on all the elective colorectal resections done at Westmead Hospital for over 2 years between 2007 and 2008. LOS, whether there was a delay in discharge because of non-medical reasons, preoperative factors such as sex, age, marital status, country of birth, use of an interpreter, any children, type of residence, use of community services, American Society of Anaesthesiology (ASA) score, and whether the patient lives on their own, is a sole carer or requires help with activities of daily living were recorded. RESULTS: Overall median age was 66 years (58­75 years). Median post-operative LOS for patients not delayed in discharge was 8 days and 15 days for patients with an identifiable non-medical reason for delay (P < 0.0001). Preoperative factors significantly associated with a delay included advanced age (odds ratio (OR): 10.5; 95% confidence interval (CI): 3.0­37.7; P < 0.0001), being widowed (OR: 3.5; 95% CI: 1.2­10.2; P = 0.02) and living in a retirement village (OR 15.4; 95% CI: 1.6­150.3; P = 0.019). Higher ASA scores strongly correlated with longer LOS. CONCLUSION: This study confirms that preoperative factors are important in contributing to non-medical delays in discharge and longer post-operative LOS after elective colorectal resections.