National Breast Cancer Foundation Research Articles

A hybrid features fusion-based framework for classification of breast micronodules using ultrasonography

BackgroundBreast cancer is one of the leading diseases worldwide. According to estimates by the National Breast Cancer Foundation, over 42,000 women are expected to die from this disease in 2024.ObjectiveThe prognosis of breast cancer depends on the early detection of breast micronodules and the ability to distinguish benign from malignant lesions. Ultrasonography is a crucial radiological imaging technique for diagnosing the illness because it allows for biopsy and lesion characterization. The user’s level of experience and knowledge is vital since ultrasonographic diagnosis relies on the practitioner’s expertise. Furthermore, computer-aided technologies significantly contribute by potentially reducing the workload of radiologists and enhancing their expertise, especially when combined with a large patient volume in a hospital setting.MethodThis work describes the development of a hybrid CNN system for diagnosing benign and malignant breast cancer lesions. The models InceptionV3 and MobileNetV2 serve as the foundation for the hybrid framework. Features from these models are extracted and concatenated individually, resulting in a larger feature set. Finally, various classifiers are applied for the classification task.ResultsThe model achieved the best results using the softmax classifier, with an accuracy of over 95%.ConclusionComputer-aided diagnosis greatly assists radiologists and reduces their workload. Therefore, this research can serve as a foundation for other researchers to build clinical solutions.

Conditional loss of Brca1 in oocytes causes reduced litter size, ovarian reserve depletion and impaired oocyte in vitro maturation with advanced reproductive age in mice

An estimated 1 in 350 women carry germline BRCA1/2 mutations, which confer an increased risk of developing breast and ovarian cancer, and may also contribute to subfertility. All mature, sex steroid-producing ovarian follicles are drawn from the pool of non-renewable primordial follicles, termed the 'ovarian reserve'. The clinical implications of early ovarian reserve exhaustion extend beyond infertility, to include the long-term adverse health consequences of loss of endocrine function and premature menopause. We aimed to determine whether conditional loss of Brca1 in oocytes impacts ovarian follicle numbers, oocyte quality and fertility in mice with advancing maternal age. We also aimed to determine the utility of AMH as a marker of ovarian function, by assessing circulating AMH levels in mice and women with BRCA1/2 mutations, and correlating this with ovarian follicle counts. In this study, we addressed a longstanding question in the field regarding the functional consequences of BRCA1 inactivation in oocytes. To recapitulate loss of BRCA1 protein function in oocytes, we generated mice with conditional gene deletion of Brca1 in oocytes using Gdf9-Cre recombinase (WT: Brca1fl/flGdf9+/+; cKO: Brca1fl/flGdf9cre/+). While the length of the fertile lifespan was not altered between groups after a comprehensive breeding trial, conditional loss of Brca1 in oocytes led to reduced litter size in female mice. Brca1 cKO animals had a reduced ovarian reserve and oocyte maturation was impaired with advanced maternal age at postnatal day (PN)300, compared to WT animals. Serum anti-Müllerian hormone (AMH) concentrations (the gold-standard indirect marker of the ovarian reserve used in clinical practice) were not predictive of reduced primordial follicle number in Brca1 cKO mice versus WT. Furthermore, we found no correlation between follicle number or density and serum AMH concentrations in matched samples from a small cohort of premenopausal women with BRCA1/2 mutations. Together, our data demonstrate that BRCA1 is a key regulator of oocyte number and quality in females and suggest that caution should be used in relying on AMH as a reliable marker of the ovarian reserve in this context. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was supported by funding from the Australian Research Council (ALW - DE21010037 and KJH - FT190100265), as well as the National Breast Cancer Foundation (IIRS-22-092) awarded to ALW and KJH. LRA, YML, LT, EOKS and MG were supported by Australian Government Research Training Program Scholarships. LRA, YML and LT were also supported by a Monash Graduate Excellence Scholarship. YC, SG and XC were supported by Monash Biomedicine Discovery Institute PhD Scholarships. LRA was also supported by a Monash University ECPF24-6809920940 Fellowship. JMS was supported by NHMRC funding (2011299). MH was supported by an NHMRC Investigator Grant (1193838).

Prediction of Abnormal Growth of Breast Cancer Cell Using Support Vector Machine

Abstract: Breast cancer is a serious health concern that affects millions of women worldwide. Early detection of breast cancer is crucial for effective treatment and improved survival rates. Artificial intelligence (AI) has shown great promise in the field of medical imaging and has been increasingly used for breast cancer detection. Cancer is one of the most dangerous diseases to humans, and yet no permanent cure has been developed for it. Breast cancer is one of the most common cancer types. According to the National Breast Cancer foundation, in 2020 alone, more than 276,000 new cases of invasive breast cancer and more than 48,000 non-invasive cases were diagnosed in the US. To put these figures in perspective, 64% of these cases are diagnosed early in the disease’s cycle, giving patients a 99% chance of survival. In this paper we develop a system for diagnosis, prognosis and prediction of breast cancer using AI. This will assist the doctors in diagnosis of the disease. In this research work, we systematically reviewed previous work done on detection and treatment of breast cancer using genetic sequencing or histopathological imaging with the help of deep learning and machine learning We use of AI for breast cancer detection, including studies that have used mammography, ultrasound, and magnetic resonance imaging (MRI) as imaging modalities. AI can also improve the accuracy and efficiency of breast cancer screening and diagnosis, as well as the challenges that must be addressed to ensure the successful integration of AI into clinical practice. However, further research and development are needed to optimize AI algorithms and ensure their safety and effectiveness in clinical practice. Breast cancer detection has emerged as a critical area of research, leveraging the power of Artificial Intelligence (AI) to enhance diagnostic accuracy and efficiency. Utilizing AI technologies, particularly deep learning, enables the development of robust and precise models for early breast cancer detection. These models analyze mammographic images, identifying subtle patterns indicative of malignancies that may escape human eye detection. Transfer learning, employing pre-trained neural network architectures, has demonstrated significant success in leveraging existing knowledge for improved performance. The integration of convolutional neural networks (CNNs) and image processing techniques empowers AI models to discern subtle abnormalities, aiding in the timely identification of potential breast tumors. Additionally, AI-driven diagnostic tools can streamline radiologists' workflow, providing rapid and reliable assessments, ultimately contributing to early intervention and improved patient outcomes. As these technologies continue to evolve, the synergy between AI and breast cancer detection promises to revolutionize screening methods, fostering a paradigm shift towards more accurate, efficient, and accessible diagnostic practices in the realm of breast health.

Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study

Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011). Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient. PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy. Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation.

Assessment of Breast Cancer Awareness Among Women of Reproductive Age in Akure South Local Government Area of Ondo State

Incidence of breast cancer is increasing worldwide. Breast cancer is the most commonly diagnosed cancer as a major cause of cancer death among woman according to national breast cancer foundation in 2016. The current prevalence of breast cancer in Nigeria is 12.5% which implies 1 out of 15 women are living with the disease. This worrisome development will continue to attract attentions and actions of governmentsat all levels, NGOs, health institutions and researchers. The study aims to assess breast cancer among women of reproductive age in Akure South Local Government Area of Ondo State. The sample size of 110 women of child-bearing age were selected randomly across Akure south, eleven political wards through multistage sampling technique. The data generated from in-depth interviews of the informants and from secondary sources like government journals, medical publications, hospital records, NGOs Articles and internet materials were qualitatively analyzed. The study revealed that majority of the respondents did not have adequate breast cancer awareness. The study concluded that the government and critical stakeholders should adopt more proactive approaches towards effective advocacy programmes that can checkmate the high mortality rate of the disease as the existing information channels have not impacted significantly on breast cancer awareness campaigns. Therefore, it is hereby recommended that governments at all levels in collaboration with NGOs, health organizations, religious bodies, mass media, traditional institutions and other stakeholders should intensify well coordinated efforts to create the needed awareness about the scourge among the womenfolk who incidentally have the highest prevalence of the disease.

Abstract P6-08-06: Uncovering gaps in patient-provider perceptions of triple-negative breast cancer care: Addressing disparities through education-advocacy partnerships

Abstract Background: Providers and patients alike are unaware of the racial disparities that exist in triple-negative breast cancer (TNBC), which occurs at twice the rate in women of the African Diaspora (WAD) compared to White American women. WAD tend to be diagnosed at a more advanced stage, use under-resourced health care settings or encounter bias in their care, and experience higher rates of TNBC-related mortality. An historically difficult-to-treat breast cancer subtype, the TNBC landscape is changing with an influx of clinical data and newly approved treatments. An educational initiative was designed to heighten awareness of new therapies, including antibody drug conjugates, empower patients in their care, and to align on addressing disparities in TNBC care. Methods: Two, 1-hour online, interactive, video-based programs were designed for patients and providers. The patient/caregiver program was hosted on CancerCoachLive in April, 2022 and the provider program on OMedLive in May, 2022 and remains on-demand until May 2023. With a focus on addressing disparities in care, 78% of patients/caregivers attending the patient program were of African descent. The initiative was conducted in collaboration with TOUCH, the Black Breast Cancer Alliance and the National Breast Cancer Foundation. Four real-world patient accounts of TNBC navigation and management were embedded in the patient program; and represented women of Caucasian, African, and Native American ethnicity. While practice and knowledge gaps among HCPs, and knowledge gaps of patients were assessed, we report on the analysis of ‘tethered’, behavioral, practice pattern, and perception questions assessed across the patient and provider programs. Results: As of June 2022, 200 providers and 29,389 patients/caregivers participated in the ongoing activities. Post education, participants in the provider program anticipated the education would positively impact practice behavior (86%) while patients/caregivers reported greater confidence in discussions with their treatment team (92%). Pre- and post-evaluation of strategies addressing disparities revealed improvements in ‘ensuring access to care through integration of care coordinators or social worker as part of the healthcare team.’ Provider assessment of barriers to enrollment in clinical trials uncovered the top barrier as ‘lack of trials at my institution’ (33%) and the top barrier to integration of new therapies as ‘lack of knowledge regarding evidence-based strategies’ (44%). Misalignments in patient-provider perceptions were observed. ‘Patient lack of interest’ was a provider-identified barrier to clinical trials, yet 60% of patients/caregivers reported that they were ‘very likely’ to participate in a clinical trial if eligible. Similarly, differences were seen in the ranking of topics of highest interest regarding treatment decisions. Lastly, patient- vs provider-identified care challenges were not aligned. Themes from the real-world patient accounts provided greater context for the misalignments observed. Conclusions: Assessment and alignment of patient-provider care perceptions has potential to impact clinical practice behaviors, patient/caregiver communication and confidence, and treatment/clinical trial knowledge for effective TNBC management. This educational partnership facilitated assessment of attitudes, perceptions, and barriers to care that can further guide how disparities in care for patients with TNBC are addressed. This ‘tethered’ approach to education was successful in empowering patients in shared decision-making, initializing changes in clinical practice, and gaining patient-provider insights in TNBC management. This activity was supported by an educational grant from Gilead Sciences, Inc Citation Format: Tariqa Ackbarali, Ricki Fairley, Tiffany A. Traina. Uncovering gaps in patient-provider perceptions of triple-negative breast cancer care: Addressing disparities through education-advocacy partnerships [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-08-06.

Impact of Breast Cancer Awareness Month on Public Interest in the United States between 2012 and 2021: A Google Trends Analysis.

Simple SummaryIn this study, we quantified public awareness regarding breast cancer associated with Breast Cancer Awareness Month (BCAM) in October using Google Trends data and a joinpoint regression analysis. We analyzed the impact of BCAM, Lung Cancer Awareness Month (LCAM), and Prostate Cancer Awareness Month (PCAM) on public awareness of the top three most common cancers in the U.S. from 2012 to 2021 using the relative search volume of Google Trends. The results imply that BCAM has successfully improved the public awareness of breast cancer in the U.S., while LCAM and PCAM had no impact on the awareness of lung and prostate cancers. BCAM could serve as a good example for organizations working on health observances or awareness campaigns.Breast Cancer Awareness Month (BCAM) has a long history of over 30 years, established in 1985 to occur every October, and the National Breast Cancer Foundation now leads the operation. There have been no studies to evaluate the impact of the BCAM on public awareness of breast cancer. We analyzed the impact of BCAM on public awareness of breast cancer in the U.S. from 2012 to 2021 using the relative search volume (RSV) of Google Trends as a surrogate. We also analyzed the impact of Lung Cancer Awareness Month (LCAM) and Prostate Cancer Awareness Month (PCAM) on public awareness of lung and prostate cancer, respectively, to see differences in their effectiveness among the health observances for the top three most common cancers in the U.S. We performed a joinpoint regression analysis to identify statistically significant time points of a change in trend. There were joinpoints around BCAM for “Breast cancer” every year from 2012 to 2021, with a significant increase in the weekly RSVs from 21.9% to 46.7%. Except for 2013 and 2015 for “Lung cancer”, when significant increases in the RSV at 1.8% and 1.2% per week were observed around LCAM, no joinpoints were noted around LCAM or PCAM. These results imply that BCAM has successfully improved the public awareness of breast cancer in the U.S. compared to other representative health observances, likely due to the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.

MP58-13 ATM MUTATIONS ARE ASSOCIATED WITH HIGH-RISK ARCHITECTURAL FEATURES IN MEN WITH FAMILIAL PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP58-13 ATM MUTATIONS ARE ASSOCIATED WITH HIGH-RISK ARCHITECTURAL FEATURES IN MEN WITH FAMILIAL PROSTATE CANCER Romy Mondschein, Bolton Damien, David Clouston, Declan Murphy, Prudence Scott, Renea Taylor, James Dowty, and Heather Thorne Romy MondscheinRomy Mondschein More articles by this author , Bolton DamienBolton Damien More articles by this author , David CloustonDavid Clouston More articles by this author , Declan MurphyDeclan Murphy More articles by this author , Prudence ScottPrudence Scott More articles by this author , Renea TaylorRenea Taylor More articles by this author , James DowtyJames Dowty More articles by this author , and Heather ThorneHeather Thorne More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002641.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Familial prostate cancer accounts for around 10% of prostate cancer diagnoses. In Australia, this represents a cohort of around 2000 men each year. Strong evidence exists that familial prostate cancers are more aggressive than sporadic cancers, best exemplified by the BRCA2 cohort. BRCA gene identification and clinical correlation with aggressive disease has allowed for modified treatment and surveillance protocols, delivering improved outcomes. Despite advances, relatively few non-BRCA germline mutations have been identified in association with prostate cancer. Lack of evidence has resulted in limited testing in a clinical setting. In this study, we aim to identify novel mutations associated with prostate cancer in a cohort of men with familial disease and correlate these mutations with clinical features of disease. METHODS: 94 families with at least two cases of verified prostate cancer were identified from within the KConFab (familial cancer) cohort. Two-thirds of families had initially been recruited due to a strong presence of breast, ovarian and colorectal cancers with limited genetic testing identifying no pathogenic mutations. Remaining families had been recruited due to multi-case prostate cancer and had not previously undergone testing. 84-cancer gene panel testing was conducted for index cases from each family, and their relatives with verified prostate cancer if the index case was found to a mutation. Clinical data including age at diagnosis, PSA, pathology stage and grade were collected for mutation carriers and non-carriers. Descriptive statistics were used to explore clinical features of each mutation. RESULTS: 9 clinically notifiable, non-BRCA, pathogenic mutations were identified (ATM n=4, HOXB13 n=3, CHEK2 n=2). ATM carriers were the largest carrier group, with nine carriers with prostate cancer confirmed across four novel ATM mutations. Mean age at diagnosis was 65 years. Six ATM carriers were stratified to the D’Amico high-risk group on the basis of Grade Group 5 pathology (n=3) or advanced stage at diagnosis (n=3). Remaining carriers were stratified into intermediate (n=2) or low risk (n=1) groups. Despite this classification, age at diagnosis for the patient in the low-risk group was just 42 years. Specialist uropathology review identified high-risk architecture (IDCP, cribiform) in four available histopathology samples. Additionally, primary lung, bladder, renal, skin (melanoma) and blood (myelodysplastic syndrome) cancers were identified among this group. CONCLUSIONS: Men with germline ATM mutations in this cohort developed high-risk prostate cancer with concerning pathological architecture. This is consistent with previous evidence associating familial prostate cancers with high-risk disease, even without germline mutations identified. Associating novel mutations with clinical disease is an important step forward in identifying those at risk of developing clinically significant cancers. Although small, in combination with further research, this data set contributes significantly to evidence for ATM gene testing in the clinical setting. Source of Funding: kConFab is supported by a grant from the National Breast Cancer Foundation and Prostate Cancer Foundation Australia © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e996 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Romy Mondschein More articles by this author Bolton Damien More articles by this author David Clouston More articles by this author Declan Murphy More articles by this author Prudence Scott More articles by this author Renea Taylor More articles by this author James Dowty More articles by this author Heather Thorne More articles by this author Expand All Advertisement PDF DownloadLoading ...

Changes in systemic cancer therapy in Australia during the COVID-19 pandemic: a population-based study.

BackgroundSince the emergence of COVID-19 there have been increasing global concerns about delays and/or discontinuations in cancer care. However, it is unclear to what extent systemic cancer therapy was impacted by COVID-19 in countries with relatively low COVID-19 infection rates. We examined changes in systemic cancer therapy in Australia during the COVID-19 pandemic.MethodsWe conducted a national observational study using de-identified records of government-subsidised cancer medicines dispensed to a random 10% sample of Australians between January 2017 to December 2020. We reported monthly dispensing and initiation rates of antineoplastic (chemo-, immuno- and targeted therapy), endocrine and supportive medicines per 100,000 population. We reported monthly discontinuation rates (defined as ≥90 days gap between cancer medicine dispensings) per 1,000 people treated. We used interrupted time series analysis to examine changes during times of increased COVID-19 risk and related public health measures (March, April and July 2020).FindingsBetween January 2017 and December 2020, 1,011,255 cancer medicines were dispensed to 51,515 people. Overall, there were no reductions in antineoplastic dispensing or initiation during the COVID-19 pandemic. In March 2020, we observed a temporary increase of 39/100,000 (95% CI: 14 to 65/100,000) in antineoplastic dispensing, driven by immunotherapy and targeted therapy. In April 2020, we observed a temporary decrease in chemotherapy initiation (-2/100,000, 95% CI: -4 to -1/100,000) and temporary increase in discontinuation of all antineoplastic medicines (35/1,000, 95% CI: 20 to 51/1,000), but these changes were not sustained.InterpretationThe effective control of COVID-19 in Australia appears to have mitigated the initial impact of COVID-19 on systemic cancer therapy. We observed only small and temporary changes in the use of some cancer medicines early in the pandemic.FundingNational Health and Medical Research Council; National Breast Cancer Foundation; Translational Cancer Research Network, supported by the Cancer Institute NSW.

Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development

Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development

The PARP inhibitor, olaparib, depletes the ovarian reserve in mice: implications for fertility preservation.

What is the impact of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, alone or in combination with chemotherapy on the ovary in mice? Olaparib treatment, when administered alone, depletes primordial follicle oocytes, but olaparib does not exacerbate chemotherapy-mediated ovarian follicle loss in mice. The ovary contains a finite number of oocytes stored within primordial follicles, which give rise to all mature ovulatory oocytes. Unfortunately, they are highly sensitive to exogenous DNA damaging insults, such as cytotoxic cancer treatments. Members of the PARP family of enzymes are central to the repair of single-strand DNA breaks. PARP inhibitors have shown promising clinical efficacy in reducing tumour burden, by blocking DNA repair capacity. Olaparib is a PARP1/2 inhibitor recently FDA-approved for treatment of BRCA1 and BRCA2 mutation carriers with metastatic breast cancer. It is currently being investigated as an adjunct to standard treatment at an earlier stage, potentially curable, BRCA1- and BRCA2-associated breast cancer which affects reproductive age women. Despite this, there is no preclinical or clinical information regarding the potential impacts of olaparib on the ovary or on female fertility. Unfortunately, it may be many years before clinical data on fertility outcomes for women treated with PARP inhibitors becomes available, highlighting the importance of rigorous preclinical research using animal models to establish the potential for new cancer therapies to affect the ovary in humans. We aimed to comprehensively determine the impact of olaparib alone, or following chemotherapy, on the ovary in mice. On Day 0, mice (n = 5/treatment group) were administered a single intraperitoneal dose of cyclophosphamide (75 mg/kg/body weight), doxorubicin (10 mg/kg), carboplatin (80 mg/kg), paclitaxel (7.5 mg/kg) or vehicle control. From Days 1 to 28, mice were administered subcutaneous olaparib (50 mg/kg) or vehicle control. This regimen is proven to reduce tumour burden in preclinical mouse studies and is also physiologically relevant for women. Adult female wild-type C57BL6/J mice at peak fertility (8 weeks) were administered a single intraperitoneal dose of chemotherapy, or vehicle, then either subcutaneous olaparib or vehicle for 28 days. Vaginal smears were performed on each animal for 14 consecutive days from Days 15 to 28 to monitor oestrous cycling. At 24 h after final treatment, ovaries were harvested for follicle enumeration and immunohistochemical analysis of primordial follicle remnants (FOXL2 expressing granulosa cells), DNA damage (γH2AX) and analysis of apoptosis by TUNEL assay. Serum was collected to measure circulating anti-Müllerian hormone (AMH) concentrations by ELISA. Olaparib significantly depleted primordial follicles by 36% compared to the control (P < 0.05) but had no impact on other follicle classes, serum AMH, corpora lutea number (indicative of ovulation) or oestrous cycling. Primordial follicle remnants were rarely detected in control ovaries but were significantly elevated in ovaries from mice treated with olaparib alone (P < 0.05). Similarly, DNA damage denoted by γH2AX foci was completely undetectable in primordial follicles of control animals but was observed in ∼10% of surviving primordial follicle oocytes in mice treated with olaparib alone. These observations suggest that functional PARPs are essential for primordial follicle oocyte maintenance and survival. Olaparib did not exacerbate chemotherapy-mediated follicle depletion in the wild-type mouse ovary. N/A. This study was performed in mice, so the findings may not translate to women and further studies utilizing human ovarian tissue and sera samples should be performed in the future. Only one long-term time point was analysed, therefore olaparib-mediated follicle damage should be assessed at more immediate time points in the future to support our mechanistic findings. Olaparib dramatically depleted primordial follicles and this could be attributed to loss of intrinsic PARP-mediated DNA repair mechanisms. Importantly, diminished ovarian reserve can result in premature ovarian insufficiency and infertility. Notably, the extent of follicle depletion might be enhanced in BRCA1 and BRCA2 mutation carriers, and this is the subject of current investigations. Together, our data suggest that fertility preservation options should be considered for young women prior to olaparib treatment, and that human studies of this issue should be prioritized. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was supported by funding from the National Health and Medical Research Council (NHMRC); (K.J.H. #1050130) (A.L.W. #1120300). K.A.P. is a National Breast Cancer Foundation Fellow (Australia-PRAC-17-004). K.A.P. is the Breast Cancer Trials (Australia) Study Chair for the OlympiA clinical trial sponsored by AstraZeneca, the manufacturer of olaparib. All other authors declare no competing financial or other interests.

Breast Cancer Awareness

As an Ob & Gyn, member of National Breast Cancer Foundation and a woman I find it very important to raise awareness about the importance of early detection of Breast Cancer. Make a difference! Spread the word about mammograms and encourage communities, organizations, your friends and family members to get involved! Your help matters. Breast cancer is the most common type of tumors among the female population of the United States. One in eight women will be diagnosed with breast cancer in their lifetime.

The Brisbane Breast Bank

The Brisbane Breast Bank (BBB) was established in 2005 with a view to collecting surplus tissue from every breast surgery patient at the Royal Brisbane and Women’s Hospital. This not-for-profit biobank provides resources on a collaborative basis, supporting local, national and international studies. The resource prides itself on its comprehensive clinico-pathology sample annotation. Since its inception, the remit of the BBB has expanded to the prospective collection of serial blood samples from patients at high risk of recurrence, and the collection of blood and tumour tissue from metastatic patients. Funding statement: RBWH Foundation Diamond Care Grant/QIMR Berghofer grant, 2014–2015. National Health and Medical Research Council (NHMRC) Program grant funding: 2007, APP006598; 2012, APP1017028; 2017, APP1113867. National Breast Cancer Foundation (NBCF) Infrastructure grant, IF-14-01, 2015.

Anti-Müllerian Hormone Serum Concentrations of Women With Germline BRCA1 or BRCA2 Mutations

Study funding/competing interest(s): kConFab is supported by a grant from the Australian National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation Practitioner Fellow. JLH is a NHMRC Senior Principal Research Fellow. MH is a NHMRC Practitioner Fellow. RA reports personal fees from Roche Diagnostics & Beckman Coulter outside the submitted work and CS reports other from Melbourne IVF outside the submitted work. The remaining authors have nothing to declare and no conflicts of interest.

TU‐H‐CAMPUS‐JeP2‐01: Inter‐Observer Delineation Comparison of Visible Glandular Breast Tissue On Magnetic Resonance Imaging and Computed Tomography (prone and Supine)

Purpose:Breast cancers predominantly arise from Glandular Breast Tissue (GBT). If the GBT can be treated effectively post‐operatively utilising radiotherapy this may be adequate volumetric coverage for adjuvant breast radiotherapy. Adequate imaging of the GBT is necessary and will be assessed between MRI and CT modalities. GBT visualisation is acknowledged to be qualitatively superior on Magnetic Resonance Image (MRI) compared to Computed Tomography (CT), the current radiotherapy imaging standard, however this has not been quantitatively assessed. For radiotherapy purposes it is important that any treatment volume can be consistently defined between observers. This study investigates the consistency of CT and MRI GBT contours for potential radiotherapy planning.Methods:Ten experts (9 breast radiation oncologists and 1 radiologist) contoured the extent of the visible GBT for 33 patients on MRI and CT (both without contrast), which was performed according to a contouring guideline in supine and prone patient positions. The GBT volume was not a conventional whole breast radiotherapy planning volume, but rather the extent of GBT that was indicated from the CT or MR imaging. Volumes were compared utilizing the dice similarity coefficient (DSC), kappa statistic, and Hausdorff Distances (HDs) to ascertain the modality that was most consistently volumed.Results:The inter‐observer concordance was of substantial agreement (kappa above 0.6) for the CT supine, CT prone, MRI supine and MRI prone datasets. The MRI GBT volumes were larger than the CT GBT volumes (p&lt;0.001). Inter‐observer conformity was higher for CT than MRI, although the magnitude of this difference was small (VOI&lt;0.04). Conformity between modalities (CT and MRI) was in agreement for both prone and supine, DSC=0.75. Prone GBT volumes were larger than supine for both MRI and CT.Conclusion:MRI improves the extent of GBT delineation. The role of MRI guided, GBT‐targeted radiotherapy requires investigation in a clinical trial.This work was supported by a grant number APP1033237 from Cancer Australia and the National Breast Cancer Foundation.

Anti-Müllerian hormone serum concentrations of women with germline BRCA1 or BRCA2 mutations.

STUDY QUESTIONDo women with BRCA1 or BRCA2 mutations have reduced ovarian reserve, as measured by circulating anti-Müllerian hormone (AMH) concentration?SUMMARY ANSWERWomen with a germline mutation in BRCA1 have reduced ovarian reserve as measured by AMH.WHAT IS KNOWN ALREADYThe DNA repair enzymes encoded by BRCA1 and BRCA2 are implicated in reproductive aging. Circulating AMH is a biomarker of ovarian reserve and hence reproductive lifespan.STUDY DESIGN, SIZE, DURATIONThis was a cross-sectional study of AMH concentrations of 693 women at the time of enrolment into the Kathleen Cuningham Foundation Consortium for research in the Familial Breast Cancer (kConFab) cohort study (recruitment from 19 August 1997 until 18 September 2012). AMH was measured on stored plasma samples between November 2014 and January 2015 using an electrochemiluminescence immunoassay platform.PARTICIPANTS/MATERIALS, SETTING, METHODSEligible women were from families segregating BRCA1 or BRCA2 mutations and had known mutation status. Participants were aged 25–45 years, had no personal history of cancer, retained both ovaries and were not pregnant or breastfeeding at the time of plasma storage. Circulating AMH was measured for 172 carriers and 216 non-carriers from families carrying BRCA1 mutations, and 147 carriers and 158 non-carriers from families carrying BRCA2 mutations. Associations between plasma AMH concentration and carrier status were tested by linear regression, adjusted for age at plasma storage, oral contraceptive use, body mass index and cigarette smoking.MAIN RESULTS AND THE ROLE OF CHANCEMean AMH concentration was negatively associated with age (P < 0.001). Mutation carriers were younger at blood draw than non-carriers (P ≤ 0.031). BRCA1 mutation carriers had, on average, 25% (95% CI: 5%–41%, P = 0.02) lower AMH concentrations than non-carriers and were more likely to have AMH concentrations in the lowest quartile for age (OR 1.84, 95% CI: 1.11–303, P = 0.02). There was no evidence of an association between AMH concentration and BRCA2 mutation status (P = 0.94).LIMITATIONS, REASONS FOR CAUTIONAMH does not directly measure the primordial follicle pool. The clinical implications of the lower AMH concentrations seen in BRCA1 mutation carriers cannot be assessed by this study design.WIDER IMPLICATIONS OF THE FINDINGSWomen with a germline mutation in BRCA1 may have reduced ovarian reserve. This is consistent with other smaller studies in the literature and has potential implications for fertility and reproductive lifespan.STUDY FUNDING/COMPETING INTEREST(S)kConFab is supported by a grant from the Australian National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. K.A.P. is an Australian National Breast Cancer Foundation Practitioner Fellow. J.L.H. is a NHMRC Senior Principal Research Fellow. M.H. is a NHMRC Practitioner Fellow. R.A.A. reports personal fees from Roche Diagnostics & Beckman Coulter outside the submitted work and C.S. reports other earnings from Melbourne IVF outside the submitted work. The remaining authors have nothing to declare and no conflicts of interest.

Angiogenesis Inhibitors in the Treatment of Breast Cancer: Exploring Avenues of New Therapeutic Targets

Breast cancer is a debilitating disease, which, according to the National Breast Cancer Foundation will affect one in eight women. While the etiology of the disease is multi factorial, angiogenesis, the growth of new vessels from pre-existing vessels, plays a central role in the progression of the disease. Over the past few decades, research has shown that angiogenesis may be the fundamental step that transitions benign tumors into malignant tumors. Endothelial cells (ECs) secrete pro-angiogenic factors that facilitate vascular network formation, thus providing tumors with the necessary oxygen and nutrients for growth and metastasis. Angiogenesis inhibitors aim to interfere with the signaling pathways that promote tumor angiogenesis. Angiogenic inhibition may be accomplished via targeting of pro-angiogenic molecules, cell surface receptors, signaling pathways, or through inhibition of other molecular events. In addition to these emerging therapies, there are several anti-angiogenic drugs that have been proven to be clinically useful in the treatment of breast cancer. It is anticipated that research with these agents will prevent the expansion of tumor masses, cause tumor dormancy, or sustain regression of the tumor. This review aims to examine some of the most recent emerging anti-angiogenic therapies along with present clinically available anti-angiogenic drugs in the treatment of breast cancer.

Abstract P1-09-09: Determination of the first evidence-based diagnosis of secondary upper limb lymphedema

Abstract Background: The incidence of secondary upper limb lymphedema after treatment for breast cancer is unclear due to the wide variety of measurement tools and diagnostic thresholds that are used in both the literature and clinical practice. Furthermore, this lack of clarity in what constitutes lymphedema or not has prevented the progression of the field of lymphedema. Many of the thresholds have been chosen for ease of use only and have no evidence base to support them. The aim of this study, therefore, was to determine which clinical diagnostic threshold for unilateral upper limb lymphedema has the best sensitivity and specificity when compared to diagnosis by lymphoscintigraphy. Methods: Women with and without a history of secondary upper limb lymphedema were assessed using lymphoscintigraphy, bioimpedance spectroscopy (BIS) as well as volume and circumference measurements using the perometer. Dermal backflow score was determined as the diagnostic criteria for the lymphoscintigraphy and was assessed by an experienced nuclear medicine physician. Determination of the presence of lymphedema by lymphoscintigraphy was compared with diagnosis by both commonly-used and normatively-determined diagnostic thresholds for circumference, volume and bioimpedance. Normatively-and commonly-used diagnostic thresholds examinedWhole arm volumeCircumferenceWhole arm BISNormatively-determined thresholds examined3SD perometry threshold*Single elevated circ (3SD threshold)*3SD Cornish, 20012SD perometry threshold*Adjacent raised circ (3SD threshold)*2SD Cornish, 20013SD frustrum threshold*Single raised threshold (2 SD)*3SD, Ward 20112SD frustum threshold*Adjacent raised circ (2SD threshold)*2SD, Ward 2011 3SD SOAC* 2SD SOAC* Commonly-used thresholds examined200 ml interlimb difference2 cm single interlimb difference 10% differenceAdjacent 2 cm interlimb difference 5 cm SOAC * Dylke et al, 2012; Sum of arm circumferences (SOAC); Circumference measure (Circ) Results: For those with widespread dermal backflow, any clinical diagnostic criteria could differentiate between those with and without lymphedema. In contrast, for those with mild to moderate dermal backflow, only the normatively-determined threshold, set at 2 standard deviations above the norm, for arm circumference and full arm bioimpedance (Cornish et al 2001) had adequate sensitivity and specificity. Both of these thresholds had clinically relevant positive (23 and 10 respectively) and negative (0.2 and 0.3) likelihood ratios. Conclusion: Evidence-based diagnostic thresholds have been established for the diagnosis of secondary upper limb lymphedema. In determining if lymphoedema is present in those with mild lymphedema, normatively-determined circumference and bioimpedance thresholds that account for limb dominance should be used. Adoption of these evidence-based criteria will allow, for the first time, comparison between studies, clarifying the incidence and risk factors for lymphedema, allowing the field to make meaningful progress forward in determining who is at-risk for lymphedema and how to prevent it from developing. Acknowledgements: Cancer Australia and National Breast Cancer Foundation. Citation Format: Sharon L Kilbreath, Elizabeth S Dylke, Geoff P Schembri, Leigh C Ward, Dale L Bailey, Deborah Black, Elizabeth A Bailey, Jane M Beith, Kathryn M Refshauge. Determination of the first evidence-based diagnosis of secondary upper limb lymphedema [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-09.

Between the baby and the breast: Translating research into practice

Those who were unable to breastfeed felt guilty about not being able to provide breast milk to their baby and sad about being denied the experience of breastfeeding. This was ameliorated by unambiguous and non-judgemental infant feeding advice given by supportive and reassuring midwives. Conclusion: This study found that most women diagnosed with GBC wish to breastfeed and demonstrates the importance of responsive midwifery care relating to infant feeding for women in this predicament. Funding gratefully acknowledged from National Breast Cancer Foundation Novel Concept Award.

Chemoprevention with the metabolism modifying drugs dichloroacetate and metformin in the Li-Fraumeni Syndrome model, Trp53 +/- mice

Supported by NHMRC Career Development Award, National Breast Cancer Foundation Novel Concept Award, and Cancer Australia.