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Advocacy in breast cancer has a history going back eight decades, influencing funding for research, giving women a voice in their treatment, and helping destigmatise the disease and its management. We aim to outline this trajectory. This is a retrospective historical narrative. We have identified a number of prominent women diagnosed with breast cancer who have had significant political influence and describe the grassroots movement of patient advocacy groups who now have a seat at the policy table and are integral to the research agenda. We also report on how as surgeons we can advocate for better treatments and care pathways, and importantly help build the evidence-base to inform better practice and policy. Surgical advocacy and consumer advocacy have led to huge improvements in management and outcomes for those affected by breast cancer., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Introduction: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management., Methods and Analysis: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used., Ethics and Dissemination: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings., Trial Registration Number: NCT05972785., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Contrast enhanced mammography (CEM) and magnetic resonance imaging (MRI) are more accurate than conventional imaging (CI) for breast cancer staging. How adding CEM and MRI to CI might change the surgical plan is understudied., Methods: Surgical plans (breast conserving surgery (BCS), wider BCS, BCS with diagnostic excision (>1BCS), mastectomy) were devised by mock-MDT (radiologist, surgeon and pathology reports) according to disease extent on CI, CI + CEM and CI + MRI. Differences in the mock-MDT's surgical plans following the addition of CEM or MRI were investigated. Using pre-defined criteria, the appropriateness of the modified plans was assessed by comparing estimated disease extent on imaging with final pathology. Surgery performed was recorded from patient records., Results: Contrast imaging modified mock-MDT plans for 20 of 61(32.8%) breasts. The addition of CEM changed the plan in 16/20 (80%) and MRI in 17/20 breasts (85%). Identical changes were proposed by both CEM and MRI in 13/20 (65%) breasts. The modified surgical plan based on CI + CEM was possibly appropriate for 6/16 (37.5%), and CI + MRI in 9/17, (52.9%) breasts. The surgery performed was concordant with the mock-MDT plan for all 10 patients where the plans could be compared (BCS 1, >1 BCS 2 and mastectomy 7)., Conclusion: Adding CEM or MRI to CI changed mock-MDT plans in up to one third of women, but not all were appropriate. Changing surgical plans following addition of contrast imaging to CI without biopsy confirmation could lead to over or under-treatment., (© 2023 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: A 2014 SSO-ASTRO guideline on surgical margins aimed to reduce unnecessary reoperation after breast conserving surgery (BCS). We investigate whether publication of the guideline was associated with a reduction in reoperation in Western Australia (WA)., Methods: In this retrospective, population-based cohort study, cases of newly-diagnosed breast cancer were identified from the WA Cancer Registry. Linkage to the Hospital Morbidity Data Collection identified index BCS for invasive cancer between January 2009 and June 2018 (N = 8059) and reoperation within 90 days. Pre-guideline (2009-2013) and post-guideline (2014-2018) reoperation proportions were compared, and temporal trends were estimated with generalised linear regression., Results: The pre-guideline reoperation proportion was 25.8% compared with 21.7% post-guideline (difference -4.0% [95% CI -5.9, -2.2, p < 0.001], odds ratio [OR] 0.80 [95% CI 0.72, 0.89, p < 0.001]). Absolute reductions were similar for repeat BCS (16.3% versus 14.6%; difference -1.8% [95% CI -3.4, -0.2, p = 0.03]) and conversion to mastectomy (9.4% versus 7.2%; difference -2.2% [95% CI -3.4, -1.0, p < 0.001]). Over the study period, there was an annual absolute change in reoperation of -0.8% (95% CI -1.2, -0.5, p < 0.001). Accounting for this linear trend, the difference in reoperation between time periods was -0.5% (95% CI -4.3, 3.3; p = 0.81), reflecting a non-significant reduction in conversion to mastectomy., Conclusions: Comparisons of pre- versus post-guideline time periods in WA showed reductions in reoperation that were similar to international estimates; however, an annual decline in reoperation predated the guideline. Analyses that do not account for temporal trends are likely to overestimate changes in reoperation associated with the guideline., Competing Interests: Declaration of competing interest MLM and NH contributed to the meta-analyses that supported the SSO/ASTRO guideline. NH contributed to the development of the SSO/ASTRO guideline. The other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate and compare the accuracy and precision of contrast-enhanced mammography (CEM) vs MRI to predict the size of biopsy-proven invasive breast cancer., Methods: Prospective study, 59 women with invasive breast cancer on needle biopsy underwent CEM and breast MRI. Two breast radiologists read each patient's study, with access limited to one modality. CEM lesion size was measured using low-energy and recombined images and on MRI, the first post-contrast series. Extent of abnormality per quadrant was measured for multifocal lesions. Reference standards were size of largest invasive malignant lesion, invasive (PathInvasive) and whole (PathTotal). Pre-defined clinical concordance ±10 mm., Results: Mean patient age 56 years, 42 (71%) asymptomatic. Lesions were invasive ductal carcinoma 40 (68%) with ductal carcinoma in situ (31/40) in 78%, multifocal in 12 (20%). Median lesion size was 17 mm (invasive) and 27 mm (total), range (5-125 mm). Lin's concordance correlation coefficients for PathTotal 0.75 (95% CI 0.6, 0.84) and 0.71 (95% CI 0.56, 0.82) for MRI and contrast-enhanced spectral mammography (CESM) respectively. Mean difference for total size, 3% underestimated and 4% overestimated, and for invasive 41% and 50% overestimate on MRI and CESM respectively. LOAs for PathTotal varied from 60% under to a 2.4 or almost threefold over estimation. MRI was concordant with PathTotal in 36 (64%) cases compared with 32 (57%) for CESM. Both modalities concordant in 26 (46%) cases respectively., Conclusion: Neither CEM nor MRI have sufficient accuracy to direct changes in planned treatment without needle biopsy confirmation., Advances in Knowledge: Despite small mean differences in lesion size estimates using CEM or MRI, the 95% limits of agreement do not meet clinically acceptable levels.

Background: Contrast-enhanced mammography (CEM) is more available than MRI for breast cancer staging but may not be as sensitive in assessing disease extent. We compared CEM and MRI in this setting., Methods: Fifty-nine women with invasive breast cancer underwent preoperative CEM and MRI. Independent pairs of radiologists read CEM studies (after reviewing a 9-case set prior to study commencement) and MRI studies (with between 5 and 25 years of experience in breast imaging). Additional lesions were assigned National Breast Cancer Centre (NBCC) scores. Positive lesions (graded NBCC ≥ 3) likely to influence surgical management underwent ultrasound and/or needle biopsy. True-positive lesions were positive on imaging and pathology (invasive or in situ). False-positive lesions were positive on imaging but negative on pathology (high-risk or benign) or follow-up. False-negative lesions were negative on imaging (NBCC < 3 or not identified) but positive on pathology., Results: The 59 women had 68 biopsy-proven malignant lesions detected on mammography/ultrasound, of which MRI demonstrated 66 (97%) and CEM 67 (99%) (p = 1.000). Forty-one additional lesions were detected in 29 patients: six of 41 (15%) on CEM only, 23/41 (56%) on MRI only, 12/41 (29%) on both; CEM detected 1/6 and MRI 6/6 malignant additional lesions (p = 0.063), with a positive predictive value (PPV) of 1/13 (8%) and 6/26 (23%) (p = 0.276)., Conclusions: While MRI and CEM were both highly sensitive for lesions detected at mammography/ultrasound, CEM may not be as sensitive as MRI in detecting additional otherwise occult foci of malignancy., Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN 12613000684729., (© 2023. Crown.)

Breast cancer is the commonest human cancer globally and one in seven Australian women will develop it in their lifetime. Surgery is the mainstay of management both for women who are at high risk of breast cancer and for those who have been diagnosed. Increased understanding of how to predict who is most at risk of breast cancer is leading to the possibility of risk-based screening, allowing better and more targeted early detection for women at high risk, and contrast imaging techniques are proving more accurate in diagnosing and staging cancer. The evolution of surgical practice includes the widespread use of oncoplastic surgery, allowing better cosmetic and oncological outcomes; reconstructive surgical advances, using free flap techniques; and sequencing of systemic and local therapies to better tailor treatments to the patient's cancer and improve outcomes. Recognition of side effects of breast cancer treatment have led to improvement in the management of conditions such as chronic pain and lymphoedema, as well as addressing the psychosocial, body image and sexual complications caused by the cancer and its treatment., (© 2022 The Author. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Significance: Imaging needles consist of highly miniaturized focusing optics encased within a hypodermic needle. The needles may be inserted tens of millimeters into tissue and have the potential to visualize diseased cells well beyond the penetration depth of optical techniques applied externally. Multimodal imaging needles acquire multiple types of optical signals to differentiate cell types. However, their use has not previously been demonstrated with live cells., Aim: We demonstrate the ability of a multimodal imaging needle to differentiate cell types through simultaneous optical coherence tomography (OCT) and fluorescence imaging., Approach: We characterize the performance of a multimodal imaging needle. This is paired with a fluorescent analog of the therapeutic drug, tamoxifen, which enables cell-specific fluorescent labeling of estrogen receptor-positive (ER+) breast cancer cells. We perform simultaneous OCT and fluorescence in situ imaging on MCF-7 ER+ breast cancer cells and MDA-MB-231 ER- cells. Images are compared against unlabeled control samples and correlated with standard confocal microscopy images., Results: We establish the feasibility of imaging live cells with these miniaturized imaging probes by showing clear differentiation between cancerous cells., Conclusions: Imaging needles have the potential to aid in the detection of specific cancer cells within solid tissue.

Background: Previous studies have suggested improved efficiency and patient outcomes with 125I seed compared with hookwire localization (HWL) in breast-conserving surgery, but high-level evidence of superior surgical outcomes is lacking. The aim of this multicentre pragmatic RCT was to compare re-excision and positive margin rates after localization using 125I seed or hookwire in women with non-palpable breast cancer., Methods: Between September 2013 and March 2018, women with non-palpable breast cancer eligible for breast-conserving surgery were assigned randomly to preoperative localization using 125I seeds or hookwires. Randomization was stratified by lesion type (pure ductal carcinoma in situ (DCIS) or other) and study site. Primary endpoints were rates of re-excision and margin positivity. Secondary endpoints were resection volumes and weights., Results: A total of 690 women were randomized at eight sites; 659 women remained after withdrawal (125I seed, 327; HWL, 332). Mean age was 60.3 years in the 125I seed group and 60.7 years in the HWL group, with no difference between the groups in preoperative lesion size (mean 13.2 mm). Lesions were pure DCIS in 25.9 per cent. The most common radiological lesion types were masses (46.9 per cent) and calcifications (28.2 per cent). The localization modality was ultrasonography in 65.5 per cent and mammography in 33.7 per cent. The re-excision rate after 125I seed localization was significantly lower than for HWL (13.9 versus 18.9 per cent respectively; P = 0.019). There were no significant differences in positive margin rates, or in specimen weights and volumes., Conclusion: Re-excision rates after breast-conserving surgery were significantly lower after 125I seed localization compared with HWL. Registration number: ACTRN12613000655741 (http://www.ANZCTR.org.au/)., (© The Author(s) 2020. Published by Oxford University Press on behalf of BJS Society Ltd.)

Guidelines endorse the use of chemoprevention for breast cancer risk reduction. This study examined the barriers and facilitators to chemoprevention use for Australian women at increased risk of breast cancer, and their clinicians. Surveys, based on the Theoretical Domains Framework, were mailed to 1,113 women at ≥16% lifetime risk of breast cancer who were enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer cohort study (kConFab), and their 524 treating clinicians. Seven hundred twenty-five women (65%) and 221 (42%) clinicians responded. Only 10 (1.4%) kConFab women had ever taken chemoprevention. Three hundred seventy-eight (52%) kConFab women, two (3%) breast surgeons, and 51 (35%) family physicians were not aware of chemoprevention. For women, the strongest barriers to chemoprevention were side effects (31%) and inadequate information (23%), which operate in the Theoretical Domains Framework domains of "beliefs about consequences" and "knowledge," respectively. Strongest facilitators related to tamoxifen's long-term efficacy (35%, "knowledge," "beliefs about consequences," and "goals" domains), staying healthy for family (13%, "social role" and "goals" domains), and abnormal breast biopsy (13%, "environmental context" domain). The strongest barrier for family physicians was insufficient knowledge (45%, "knowledge" domain) and for breast surgeons was medication side effects (40%, "beliefs about consequences" domain). The strongest facilitators for both clinician groups related to clear guidelines, strong family history, and better tools to select patients ("environmental context and resources" domain). Clinician knowledge and resources, and beliefs about the side-effect consequences of chemoprevention, are key domains that could be targeted to potentially enhance uptake. PREVENTION RELEVANCE: Despite its efficacy in reducing breast cancer incidence, chemoprevention is underutilised. This survey study of Australian women and their clinicians used behavioural change theory to identify modifiable barriers to chemoprevention uptake, and to suggest interventions such as policy change, educational resources and public campaigns, that may increase awareness and use. See related Spotlight by Vogel, p. 1 ., (©2020 American Association for Cancer Research.)

Compression optical coherence elastography (OCE) typically requires a mechanical actuator to impart a controlled uniform strain to the sample. However, for handheld scanning, this adds complexity to the design of the probe and the actuator stroke limits the amount of strain that can be applied. In this work, we present a new volumetric imaging approach that utilizes bidirectional manual compression via the natural motion of the user's hand to induce strain to the sample, realizing compact, actuator-free, handheld compression OCE. In this way, we are able to demonstrate rapid acquisition of three-dimensional quantitative microelastography (QME) datasets of a tissue volume (6 × 6 × 1 mm 3 ) in 3.4 seconds. We characterize the elasticity sensitivity of this freehand manual compression approach using a homogeneous silicone phantom and demonstrate comparable performance to a benchtop mounted, actuator-based approach. In addition, we demonstrate handheld volumetric manual compression-based QME on a tissue-mimicking phantom with an embedded stiff inclusion and on freshly excised human breast specimens from both mastectomy and wide local excision (WLE) surgeries. Tissue results are coregistered with postoperative histology, verifying the capability of our approach to measure the elasticity of tissue and to distinguish stiff tumor from surrounding soft benign tissue., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Effective intraoperative tumor margin assessment is needed to reduce re-excision rates in breast-conserving surgery (BCS). Mapping the attenuation coefficient in optical coherence tomography (OCT) throughout a sample to create an image (attenuation imaging) is one promising approach. For the first time, three-dimensional OCT attenuation imaging of human breast tissue microarchitecture using a wide-field (up to ~45 × 45 × 3.5 mm) imaging system is demonstrated. Representative results from three mastectomy and one BCS specimen (from 31 specimens) are presented with co-registered postoperative histology. Attenuation imaging is shown to provide substantially improved contrast over OCT, delineating nuanced features within tumors (including necrosis and variations in tumor cell density and growth patterns) and benign features (such as sclerosing adenosis). Additionally, quantitative micro-elastography (QME) images presented alongside OCT and attenuation images show that these techniques provide complementary contrast, suggesting that multimodal imaging could increase tissue identification accuracy and potentially improve tumor margin assessment., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate. This study determined, for the first time, the diagnostic accuracy of quantitative micro-elastography (QME), an optical coherence tomography (OCT)-based elastography technique that produces images of tissue microscale elasticity, for detecting tumor within 1 mm of the margins of BCS specimens. Simultaneous OCT and QME were performed on the margins of intact, freshly excised specimens from 83 patients undergoing BCS and on dissected specimens from 7 patients undergoing mastectomy. The resulting three-dimensional images (45 × 45 × 1 mm) were coregistered with postoperative histology to determine tissue types present in each scan. Data from 12 BCS patients and the 7 mastectomy patients served to build a set of images for reader training. One hundred and fifty-four subimages (10 × 10 × 1 mm) from the remaining 71 BCS patients were included in a blinded reader study, which resulted in 69.0% sensitivity and 79.0% specificity using OCT images, versus 92.9% sensitivity and 96.4% specificity using elasticity images. The quantitative nature of QME also facilitated development of an automated reader, which resulted in 100.0% sensitivity and 97.7% specificity. These results demonstrate high accuracy of QME for detecting tumor within 1 mm of the margin and the potential for this technique to improve outcomes in BCS. SIGNIFICANCE: An optical imaging technology probes breast tissue elasticity to provide accurate assessment of tumor margin involvement in breast-conserving surgery., (©2020 American Association for Cancer Research.)

Objective: TARGIT-A randomised women with early breast cancer to receive external beam radiotherapy (EBRT) or intraoperative radiotherapy (TARGIT-IORT). This study aimed to identify what extra risk of recurrence patients would accept for perceived benefits and risks of different radiotherapy treatments., Methods: Patient preferences were determined by self-rated trade-off questionnaires in two studies: Stage (1) 209 TARGIT-A participants (TARGIT-IORTn = 108, EBRTn = 101); Stage (2) 123 non-trial patients yet to receive radiotherapy (pre-treatment group), with 85 also surveyed post-radiotherapy. Patients traded-off risks of local recurrence in preference selection between TARGIT-IORT and EBRT., Results: TARGIT-IORT patients were more accepting of IORT than EBRT patients with 60% accepting the highest increased risk presented (4%-6%) compared to 12% of EBRT patients, and 2% not accepting IORT at all compared to 43% of EBRT patients. Pre-treatment patients were more accepting of IORT than post-treatment patients with 23% accepting the highest increased risk presented compared to 15% of post-treatment patients, and 15% not accepting IORT at all compared to 41% of pre-treatment patients., Conclusions: Breast cancer patients yet to receive radiotherapy accept a higher recurrence risk than the actual risk found in TARGIT-A. Measured patient preferences are highly influenced by experience of treatment received. This finding challenges the validity of post-treatment preference studies., (© 2019 The Authors. European Journal of Cancer Care Published by John Wiley & Sons Ltd.)

Accurate and effective removal of tumor in one operation is an important goal of breast-conserving surgery. However, it is not always achieved. Surgeons often utilize manual palpation to assess the surgical margin and/or the breast cavity. Manual palpation, however, is subjective and has relatively low resolution. Here, we investigate a tactile imaging technique, optical palpation, for the visualization of tumor. Optical palpation generates maps of the stress at the surface of tissue under static preload compression. Stress is evaluated by measuring the deformation of a contacting thin compliant layer with known mechanical properties using optical coherence tomography. In this study, optical palpation is performed on 34 freshly excised human breast specimens. Wide field-of-view (up to ~46 × 46 mm) stress images, optical palpograms, are presented from four representative specimens, demonstrating the capability of optical palpation to visualize tumor. Median stress reported for adipose tissue, 4 kPa, and benign dense tissue, 8 kPa, is significantly lower than for invasive tumor, 60 kPa. In addition, we demonstrate that optical palpation provides contrast consistent with a related optical technique, quantitative micro-elastography. This study demonstrates that optical palpation holds promise for visualization of tumor in breast-conserving surgery., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The purpose of this research was to assess agreement between four rating systems of cosmetic outcome measured in a subset of patients with early breast cancer participating in the randomised TARGIT-A trial. TARGIT-A compared risk-adapted single-dose intra-operative radiotherapy (TARGIT-IORT) to whole breast external beam radiotherapy (EBRT)., Methods: Patients, their Radiation Oncologist and Research Nurse completed a subjective cosmetic assessment questionnaire before radiotherapy and annually thereafter for five years. Objective data previously calculated by the validated BCCT.core software which utilizes digital photographs to score symmetry, colour and scar was also used. Agreement was assessed by the Kappa statistic and longitudinal changes were assessed by generalized estimating equations., Results: Overall, an Excellent-Good (EG) cosmetic result was scored more often than a Fair-Poor (FP) result for both treatment groups across all time points, with patients who received TARGIT-IORT scoring EG more often than those who received EBRT however this was statistically significant at Year 5 only. There was modest agreement between the four rating systems with the highest Kappa score being moderate agreement which was between nurse and doctor scores at Year 1 with Kappa = 0.46 (p < 0.001), 95% CI (0.24, 0.68)., Conclusion: Despite similar overall findings between treatment groups and rating systems, the inter-rater agreement was only modest. This suggests that the four rating systems utilized may not necessarily be used interchangeably and it is arguable that for an outcome such as cosmetic appearance, the patient's point of view is the most important., Trial Registration: TARGIT-A ISRCTN34086741 , Registered 21 July 2004, retrospectively registered.

More than 6 million women worldwide are living with a past diagnosis of breast cancer. Most survive their illness, and management of the long-term consequences of treatment has become a priority in cancer care. Menopausal symptoms affect most breast cancer survivors and may significantly impair quality of life. We describe a multidisciplinary model to evaluate and manage these women using a patient-focused approach. The 'Multidisciplinary Menopause After Cancer Clinic' includes gynecologists, endocrinologists, GPs, a psychologist and a clinical nurse specialist. Benefits of this model include improved coordination of patient care, education, communication and evidence-based decision making., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for 'confounding by indication' was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03-1.15, I 2 =0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94-1.03, I 2 =35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We thus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Surgical treatment of breast cancer aims to identify and remove all malignant tissue. Intraoperative assessment of tumor margins is, however, not exact; thus, re-excision is frequently needed, or excess normal tissue is removed. Imaging methods applicable intraoperatively could help to reduce re-excision rates whilst minimizing removal of excess healthy tissue. Optical coherence elastography (OCE) has been proposed for use in breast-conserving surgery; however, intraoperative interpretation of complex OCE images may prove challenging. Observations of breast cancer on multiple length scales, by OCE, ultrasound elastography, and atomic force microscopy, have shown an increase in the mechanical heterogeneity of malignant breast tumors compared to normal breast tissue. In this study, a micro-scale mechanical heterogeneity index is introduced and used to form heterogeneity maps from OCE scans of 10 ex vivo human breast tissue samples. Through comparison of OCE, optical coherence tomography images, and corresponding histology, malignant tissue is shown to possess a higher heterogeneity index than benign tissue. The heterogeneity map simplifies the contrast between tumor and normal stroma in breast tissue, facilitating the rapid identification of possible areas of malignancy, which is an important step towards intraoperative margin assessment using OCE., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Evaluation of lymph node involvement is an important factor in detecting metastasis and deciding whether to perform axillary lymph node dissection (ALND) in breast cancer surgery. As ALND is associated with potentially severe long term morbidity, the accuracy of lymph node assessment is imperative in avoiding unnecessary ALND. The mechanical properties of malignant lymph nodes are often distinct from those of normal nodes. A method to image the micro-scale mechanical properties of lymph nodes could, thus, provide diagnostic information to aid in the assessment of lymph node involvement in metastatic cancer. In this study, we scan axillary lymph nodes, freshly excised from breast cancer patients, with optical coherence micro-elastography (OCME), a method of imaging micro-scale mechanical strain, to assess its potential for the intraoperative assessment of lymph node involvement., Methods: Twenty-six fresh, unstained lymph nodes were imaged from 15 patients undergoing mastectomy or breast-conserving surgery with axillary clearance. Lymph node specimens were bisected to allow imaging of the internal face of each node. Co-located OCME and optical coherence tomography (OCT) scans were taken of each sample, and the results compared to standard post-operative hematoxylin-and-eosin-stained histology., Results: The optical backscattering signal provided by OCT alone may not provide reliable differentiation by inspection between benign and malignant lymphoid tissue. Alternatively, OCME highlights local changes in tissue strain that correspond to malignancy and are distinct from strain patterns in benign lymphoid tissue. The mechanical contrast provided by OCME complements the optical contrast provided by OCT and aids in the differentiation of malignant tumor from uninvolved lymphoid tissue., Conclusion: The combination of OCME and OCT images represents a promising method for the identification of malignant lymphoid tissue. This method shows potential to provide intraoperative assessment of lymph node involvement, thus, preventing unnecessary removal of uninvolved tissues and improving patient outcomes.

Objective: The aim of the study was to determine the association between adjuvant chemotherapy for breast cancer and menopausal symptoms, sexual function, and quality of life., Methods: Participants attended a menopause clinic with a dedicated service for cancer survivors at a large tertiary women's hospital. Information about breast cancer treatments including adjuvant chemotherapy was collected from medical records. Menopausal symptoms were recorded with the Greene Climacteric Scale and Functional Assessment of Cancer Therapy, Breast Cancer, and Endocrine Symptom Subscales. Sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. Quality of life was measured with Functional Assessment of Cancer Therapy scales., Results: The severity of vasomotor, psychological, or sexual symptoms (apart from pain) did not differ between those who had received adjuvant chemotherapy (n = 339) and other breast cancer survivors (n = 465). After adjustment for current age, time since menopause, and current use of antiestrogen endocrine therapy, the risk of "severe pain" with sexual intercourse was twice as common after chemotherapy (31.6% vs 20.0%, odds ratio [OR] 2.18, 95% CI 1.25-3.79). Those treated with chemotherapy were more likely to report "severe problems" with physical well-being (OR 1.92, 95% CI 1.12-3.28) and lower breast cancer-specific quality of life (OR 1.89 95% CI 1.13-3.18), but did not differ in other quality of life measures., Conclusions: In this large study of breast cancer patients presenting to a specialty menopause clinic, previous chemotherapy was not associated with current vasomotor or psychological symptoms. Severe pain with intercourse was significantly more common in those treated with adjuvant chemotherapy.

Purpose: To report the first comprehensive investigation of patient-reported cosmesis and breast-related quality of life (QOL) outcomes comparing patients randomized to risk-adapted single-dose intraoperative radiation therapy (TARGIT-IORT) versus external beam radiation therapy (EBRT) on the TARGIT-A trial., Methods and Materials: Longitudinal cosmesis and QOL data were collected from a subset of TARGIT-A participants who received TARGIT-IORT as a separate procedure (postpathology). Patients completed a cosmetic assessment before radiation therapy and annually thereafter for at least 5 years. Patients also completed the combined European Organization for Research and Treatment of Cancer (EORTC) core questionnaire and Breast-Specific Module in addition to the Body Image after Breast Cancer Questionnaire at baseline and annually thereafter. The combined EORTC questionnaires were also collected 3, 6, and 9 months after wide local excision., Results: An Excellent-Good cosmetic result was scored more often than a Fair-Poor result for both treatment groups across all time points. The TARGIT-IORT patients reported better breast-related QOL than EBRT patients. Statistically and clinically significant differences were seen at month 6 and year 1, with EBRT patients having moderately worse breast symptoms (a statistically significant difference of more than 10 in a 100-point scale) than TARGIT-IORT patients at these time points., Conclusion: Patients treated with TARGIT-IORT on the TARGIT-A trial have similar self-reported cosmetic outcome but better breast-related QOL outcomes than patients treated with EBRT. This important evidence can facilitate the treatment decision-making process for patients who have early breast cancer suitable for breast-conserving surgery and inform their clinicians., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs.

Probing the mechanical properties of tissue on the microscale could aid in the identification of diseased tissues that are inadequately detected using palpation or current clinical imaging modalities, with potential to guide medical procedures such as the excision of breast tumours. Compression optical coherence elastography (OCE) maps tissue strain with microscale spatial resolution and can delineate microstructural features within breast tissues. However, without a measure of the locally applied stress, strain provides only a qualitative indication of mechanical properties. To overcome this limitation, we present quantitative micro-elastography, which combines compression OCE with a compliant stress sensor to image tissue elasticity. The sensor consists of a layer of translucent silicone with well-characterized stress-strain behaviour. The measured strain in the sensor is used to estimate the two-dimensional stress distribution applied to the sample surface. Elasticity is determined by dividing the stress by the strain in the sample. We show that quantification of elasticity can improve the ability of compression OCE to distinguish between tissues, thereby extending the potential for inter-sample comparison and longitudinal studies of tissue elasticity. We validate the technique using tissue-mimicking phantoms and demonstrate the ability to map elasticity of freshly excised malignant and benign human breast tissues.

An accurate intraoperative identification of malignant tissue is a challenge in the surgical management of breast cancer. Imaging techniques that help address this challenge could contribute to more complete and accurate tumor excision, and thereby help reduce the current high reexcision rates without resorting to the removal of excess healthy tissue. Optical coherence microelastography (OCME) is a three-dimensional, high-resolution imaging technique that is sensitive to microscale variations of the mechanical properties of tissue. As the tumor modifies the mechanical properties of breast tissue, OCME has the potential to identify, on the microscale, involved regions of fresh, unstained tissue. OCME is based on the use of optical coherence tomography (OCT) to measure tissue deformation in response to applied mechanical compression. In this feasibility study on 58 ex vivo samples from patients undergoing mastectomy or wide local excision, we demonstrate the performance of OCME as a means to visualize tissue microarchitecture in benign and malignant human breast tissues. Through a comparison with corresponding histology and OCT images, OCME is shown to enable ready visualization of features such as ducts, lobules, microcysts, blood vessels, and arterioles and to identify invasive tumor through distinctive patterns in OCME images, often with enhanced contrast compared with OCT. These results lay the foundation for future intraoperative studies. Cancer Res; 75(16); 3236-45. ©2015 AACR., (©2015 American Association for Cancer Research.)

Background: A significant proportion of breast cancers present as impalpable lesions requiring radiological guidance prior to surgical excision, commonly by hook-wire placement. Complete lesion excision is an essential part of treatment, and re-excision may be needed to ensure this and minimize local recurrence. We explore a 1-year audit of re-excision of hook-wire-guided excisions in two large public breast units in Western Australia and define factors associated with the requirement for re-excision., Methods: A retrospective review of wire-localized wide local excisions for early breast cancer in 2009 at two tertiary breast centres in Western Australia., Results: Of 148 localized lesions, 44 (30%) underwent re-excision. The only significant preoperative finding was the location of tumour in the breast. The intra-operative specimen radiograph provided useful information that influenced re-excision. Smaller (≤5 mm) and larger (>20 mm) tumours on final pathological size were more likely to undergo re-excision as well as a larger difference in actual size to predicted size. The presence of ductal carcinoma in situ (DCIS) increased re-operation, as did multifocality., Conclusion: This study highlights factors that should make the surgeon more cautious for re-excision. Suspicion of DCIS, especially at the periphery of tumours, and a central tumour location increase risk. Lesion localization techniques play an important role in minimizing risk while maintaining cosmesis., (© 2015 Royal Australasian College of Surgeons.)

Objective: The purpose of this study was to evaluate a new imaging technique for the assessment of breast cancer tumor margins. The technique entails deployment of a high-resolution optical imaging needle under ultrasound guidance. Assessment was performed on fresh ex vivo tissue samples., Conclusion: Use of the ultrasound-guided optical needle probe allowed in situ assessment of fresh tissue margins. The imaging findings corresponded to the histologic findings.

Objective: The aim of this study was to describe a unique model of multidisciplinary care for women with menopausal symptoms after breast cancer and present preliminary data for 653 women., Methods: The nature and severity of menopausal symptoms in women with breast cancer were measured using a standardized scale., Results: A total of 578 women with breast cancer were managed at the Menopausal Symptoms After Cancer Clinic between January 2003 and December 2008. The most common reasons for these women to seek treatment were hot flushes (41%), night sweats (36%), loss of interest in sex (30%), difficulty sleeping (25%), and fatigue (22%). Extreme vaginal dryness was also reported in 19% of these women. Chemotherapy-induced ovarian failure was reported by 29% of the breast cancer patients seen. A range of management approaches were offered, with 55% of the women prescribed nonhormonal pharmacological therapies for vasomotor symptoms, including vitamin E 400 IU twice daily (21%), venlafaxine 75 mg CR once daily (13%), clonidine 50 microg twice daily (11%), or gabapentin 300 mg three times daily (4%)., Conclusions: Vasomotor symptoms, sexual dysfunction, and sleep disturbance are the most distressing menopausal symptoms requiring management after breast cancer. Menopausal symptom management after breast cancer may be complex, and we present a novel model of care using a multidisciplinary approach. Additional benefits of this multidisciplinary approach include education opportunities, improved communication and networking opportunities, and decision making in line with evidence-based guidelines.

Objective: To determine whether a surveillance program including clinical breast examination (CBE) and three screening modalities (magnetic resonance imaging [MRI], high-resolution ultrasound [U/S] and mammographic x-ray [MMX]) was feasible, and whether it could improve detection of pathological lesions in young women at high risk of developing breast cancer., Design, Setting and Participants: Western Australian women aged 50 years or under at high risk of developing breast cancer were recruited to our study. For a 2-year period, they were offered breast MRI and U/S scans in addition to their annual MMX and CBE. Our study was conducted between June 2002 and October 2005., Main Outcome Measures: Number and type of cancerous or precancerous lesions; recall rates after screening; comparative sensitivity of screening modalities., Results: Of 102 women approached, 72 agreed to participate. Fifteen lesions were detected, of which three were significant: a metastatic papillary cancer in an axillary lymph node, a borderline lesion (multiple papillomatosis with atypia), and a papilloma. All 15 lesions were visible on MRI, and four were detected by MRI only. Only one lesion was visible on all three imaging modalities. Nothing significant was detected by CBE. The recall rate after MRI scans fell from 9/72 (12.5%) in the first year to 5/67 (7.5%) in the second year., Conclusion: Our study gave valuable experience in a team approach to screening MRI, and showed that MRI can detect more lesions than MMX or U/S in women at high risk of developing breast cancer. Screening U/S may not add value to MMX and MRI screening, and we suggest a single oblique-view MMX may be used in some cases.

Background: Breast cancer is the most common cancer in women in developed countries, and 12% of breast cancer occurs in women 20-34 years. Survival from breast cancer has significantly improved, and the potential late effects of treatment and the impact on quality of life have become increasingly important. Young women constitute a minority of breast cancer patients, but commonly have distinct concerns and issues compared with older women, including queries regarding fertility, contraception and pregnancy. Further, they are more likely than older women to have questions regarding potential side effects of therapy and risk of relapse or a new primary. In addition, many will have symptoms associated with treatment and they present a management challenge. Reproductive medicine specialists and gynaecologists commonly see these women either shortly after initial diagnosis or following adjuvant therapy and should be aware of current management of breast cancer, the options for women at increased genetic risk, the prognosis of patients with early stage breast cancer and how adjuvant systemic treatments may impact reproductive function., Methods: No systematic literature search was done. The review focuses on the current management of breast cancer in young women and the impact of treatment on reproductive function and subsequent management. With reference to key studies and meta-analyses, we highlight controversies and current unanswered questions regarding patient management., Results: Chemotherapy for breast cancer is likely to negatively impact on reproductive function. A number of interventions are available which may increase the likelihood of future successful pregnancy, but the relative safety of these interventions is not well established. For those who do conceive following breast cancer, there is no good evidence that pregnancy is detrimental to survival. We review current treatment; effects on reproductive function; preservation of fertility; contraception; pregnancy; breastfeeding and management of menopausal symptoms following breast cancer., Conclusion: This paper provides an update on the management of breast cancer in young women and is targeted at reproductive medicine specialists and gynaecologists.

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.

Increasing numbers of women have menopausal symptoms after treatment for breast cancer. These symptoms can result directly from cancer treatments (such as oophorectomy, ovarian suppression, chemotherapy-induced ovarian failure, and antioestrogens), as a spontaneous event, or after discontinuation of hormone-replacement therapy. The onset of menopausal symptoms after treatment for breast cancer can have a long-lasting effect on quality of life, body image, sexual function, and self esteem. Hormone-replacement therapy that contains oestrogen is the most effective treatment for menopausal symptoms in healthy women. However, evidence from one randomised controlled trial suggests that use of hormone replacement therapy after breast cancer raises the risk of recurrence and of new primary breast cancer. As the incidence of breast cancer increases and survival continues to improve, the number of women with menopausal symptoms will probably rise. Safe and effective non-hormonal treatments for severe menopausal symptoms after breast cancer are urgently needed. Few studies have addressed the management of menopausal symptoms after breast cancer, and the quality of studies is generally poor. Progestagens, and selective inhibitors of serotonin and norepinephrine reuptake seem to offer reasonable symptom palliation, but the long-term effectiveness and safety of these preparations is not known. We propose that the management of menopausal symptoms in patients with a history of cancer requires a patient-centred, but multidisciplinary, approach.

This descriptive population-based study estimates the incidence, and describes the management and outcomes for women diagnosed with gestational breast cancer (GBC) aged 15-44 years in Western Australia between January 1982 and December 2000. Gestational breast cancer accounted for 6.25% of breast cancers in Western Australian women less than 45 years of age, and complicated 23.6 per 100,000 pregnancies. Two thirds were diagnosed postpartum and a third while pregnant. The median time from first symptom to diagnosis was less than four weeks. Women diagnosed during pregnancy were more likely to have a pregnancy termination. Over 50% of women were lymph node positive and those diagnosed postpartum were more likely to have a mastectomy. Five-year survival was better than reported previously (73%). The incidence of GBC was lower than previously reported. Significant differences in pregnancy outcome and management exist between the pregnant and postpartum groups.

Background: Mortality rates from breast cancer are stabilizing or falling in many developed countries including Australia, however, survival outcomes are known to vary by social, demographic and treatment related factors. The aim of the present study was to investigate how hospital, social and demographic factors were associated with survival outcomes from surgically treated breast cancer for all women living in Western Australia., Methods: The WA Data Linkage System was used to access hospital morbidity, death and cancer information for all women diagnosed with invasive breast cancer in Western Australia 1982-2000. Relative survival and Cox proportional hazards regression analyses were used to identify social, demographic and hospital factors associated with an increased risk of dying from breast cancer or dying from any cause., Results: Survival outcomes improved in all women diagnosed in more recent calendar periods. However, a significantly increased risk of dying was observed for women who underwent initial surgical treatment in regional public hospitals outside of the state capital, Perth. Consistent with other reports, women aged greater than 80 years and younger than 35 years at diagnosis also had poorer survival outcomes. Residential location, socioeconomic status and race were not associated with survival after adjusting for treatment, health and hospital related factors., Conclusions: Despite overall improvements in survival of women diagnosed with breast cancer in Western Australia, initial surgical treatment in public hospitals outside of Perth was associated with significantly poorer outcomes.

Background: In line with current Australian early breast cancer management guidelines, more women are having breast conserving surgery to treat breast cancer when appropriate. Some women will undergo further surgery because of involved margins, early local relapse, or other factors including patient choice. The aim of this study was to investigate whether socio-economic, demographic or hospital factors were associated with the risk of re-excision or subsequent mastectomy., Methods: A record linkage population-based study on 12 711 women diagnosed with breast cancer in Western Australia from 1982 to 2000 who underwent breast surgery within 12 months of diagnosis was performed. Logistic regression was used to identify social, demographic and hospital factors associated with the risk of undergoing further surgery following initial breast conserving surgery., Results: The proportion of women undergoing initial breast conserving surgery doubled from 33% in 1982-1985 to 72% in 1998-2000. The proportion of women who underwent further surgery following initial breast conserving surgery decreased from 50 to 30% over the same period. The risk of re-excision or subsequent mastectomy was between 2.4 (95% CI 1.7-3.4) and 5.0 (95% CI 3.4-7.4) times greater if initial surgery was performed in a non-metropolitan hospital compared to Perth hospitals. Younger women were between 1.7 (95% CI 1.4-2.0) and 2.1 (95% CI 1.5-3.0) times more likely to undergo re-excisions compared to women aged 50-64 years of age., Conclusions: Young women and women initially treated in non-metropolitan hospitals were at an increased risk of re-excision or a subsequent mastectomy following initial breast conserving surgery to treat breast cancer. Efforts need to be directed towards improving specialist health services outside of Perth if women continue to be treated for breast cancer in non-metropolitan hospitals.

Background: A new device, Intrabeam, is available for intraoperative radiotherapy. We have prospectively examined its feasibility and tolerability in delivering adjuvant breast cancer treatment., Methods: Thirty-five patients undergoing breast-conserving surgery received targeted tumour bed irradiation consisting of 5 Gy (at 10 mm) in a single fraction. This single intraoperative treatment was used to replace the external beam radiotherapy "boost" that would usually be given in 10 daily treatments following 5 weeks of whole breast irradiation. Patients later completed external beam radiotherapy as usual. Potential toxicities were prospectively assessed fortnightly prior to external beam radiotherapy, weekly during it, and 3 monthly subsequently., Results: The intraoperative radiotherapy was able to be delivered without difficulty, either at time of initial cancer surgery or as a second procedure. When performed as a separate procedure the median operating time was 56 min. The treatment was well tolerated, with only one patient experiencing any grade 3 or 4 toxicities--this was acute grade three itch. There was an overall early breast infection rate of 17%. No unexpected toxicities were seen., Conclusions: This simple and well-tolerated treatment delivers a useful radiation dose to the area of highest risk of tumour recurrence. The early infection rate is similar to that reported in the literature, for treatments without intraoperative radiotherapy. Whether such a treatment may adequately replace the entire adjuvant radiation therapy treatment for low-risk patients is now being studied in a randomized trial.

Background: The purpose of the present paper was to review the current knowledge of pregnancy concurrent with a diagnosis of breast cancer, and how best to manage this group of women and those breast cancer survivors who may subsequently conceive., Results: Pregnancy-associated breast cancer or gestational breast cancer is defined as breast cancer diagnosed during pregnancy or in the 12 months post-partum. A review of the current literature on breast cancer-related pregnancy suggests an incidence of between 0.7 and 3.9%. The prognosis is thought not to be significantly different from non-pregnancy-associated breast cancer, except in cases where a delay in diagnosis is associated with more advanced disease. The treatment is similar to non-pregnant cases, with the exception of radiotherapy, which is contraindicated throughout pregnancy; and chemotherapy, which is contraindicated during the first trimester. Few breast cancer survivors go on to conceive, but those who do have no worse breast cancer or pregnancy outcomes., Conclusion: Most of the research in this field has come from small, specialized institutions and may not reflect what occurs in the wider community. Further population-based research in this area is needed, and is currently being undertaken in Western Australia.

Hormonal therapies for cancer are often viewed as a gentler option than many other cancer treatments, but is low toxicity an accurate perception of patients' experiences? Side effects tend to be described as minimal or well tolerated, yet published symptoms from hormonal therapy vary considerably in their descriptions and frequencies. Previous research has highlighted under-reporting of side effects by clinical staff so as part of a wider study examining tamoxifen and goserelin treatment as adjuvant therapy for breast cancer, treatment-related symptoms documented in medical notes were compared with those that patients reported during a research interview. There was a significant difference in the frequency of many side effects reported by the two methods in this study. Sixty four out of 72 (89%) women who had received adjuvant tamoxifen or goserelin had side effects recorded in their medical notes, compared with 74/75 (99%) reporting side effects at interview. We compared the published frequencies of commonly reported symptoms with those found ourselves. The discrepancies between patient-reported and clinician-recorded (usually from clinical trial data) symptom profiles were similar to those found in our study. Without accurate comprehensive side effect profiles for hormone therapies, prospective patients cannot make informed judgements on proposed treatments.

The last decade has seen many changes in the management of breast cancer, both in surgical treatment and in systemic therapy, which can reduce the mortality rate by 25%. At the same time attention has turned to improving not only length of survival but also quality of life. These changes plus new developments in breast cancer treatment are reviewed here.