Surgery (RMH) - Research Publications

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    Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer
    Partridge, AH ; Niman, SM ; Ruggeri, M ; Peccatori, FA ; Azim, HA ; Colleoni, M ; Saura, C ; Shimizu, C ; Saetersdal, AB ; Kroep, JR ; Mailliez, A ; Warner, E ; Borges, VF ; Amant, F ; Gombos, A ; Kataoka, A ; Rousset-Jablonski, C ; Borstnar, S ; Takei, J ; Lee, JE ; Walshe, JM ; Ruiz-Borrego, M ; Moore, HCF ; Saunders, C ; Bjelic-Radisic, V ; Susnjar, S ; Cardoso, F ; Smith, KL ; Ferreiro, T ; Ribi, K ; Ruddy, K ; Kammler, R ; El-Abed, S ; Viale, G ; Piccart, M ; Korde, LA ; Goldhirsch, A ; Gelber, RD ; Pagani, O (MASSACHUSETTS MEDICAL SOC, 2023-05-04)
    BACKGROUND: Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. METHODS: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. RESULTS: Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. CONCLUSIONS: Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).
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    Surviving and thriving after breast cancer treatment
    Saunders, CM ; Stafford, L ; Hickey, M (WILEY, 2022-09-05)
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    Healthcare professionals' views on how palliative care should be delivered in Bhutan: A qualitative study.
    Laabar, TD ; Saunders, C ; Auret, K ; Johnson, CE ; García Peña, C (Public Library of Science (PLoS), 2022)
    Palliative care aims to relieve serious health-related suffering among patients and families affected by life-limiting illnesses. However, palliative care remains limited or non-existent in most low- and middle- income countries. Bhutan is a tiny kingdom in the Himalayas where palliative care is an emerging concept. This study aimed to explore the views of Bhutanese healthcare professionals on how palliative care should be delivered in Bhutan. It is a component of a bigger research program aimed at developing a contextual based palliative care model for Bhutan. This is a descriptive qualitative study. Eleven focus group discussions and two in-depth interviews were conducted among healthcare professionals, recruited through purposeful sampling, from community health centres, district hospitals, regional and national referral hospitals, and the traditional hospital in Bhutan. The participants in this study emphasized the need for suitable palliative care policies; education, training and awareness on palliative care; adequate access to essential palliative care medicines; adequate manpower and infrastructure; and a multi-disciplinary palliative care team. Participants confirmed a socially, culturally and spiritually appropriate approach is crucial for palliative care services in Bhutan. Despite palliative care being a young concept, the Bhutanese healthcare professionals have embraced its importance, emphasized its urgent need and highlighted their views on how it should be delivered in the country. This study will help inform the development of a public health-focused palliative care model, socially, culturally and spiritually applicable to the Bhutanese people, as recommended by the World Health Organization.
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    Perinatal outcomes of women with gestational breast cancer in Australia and New Zealand: A prospective population-based study
    Sullivan, E ; Safi, N ; Li, Z ; Remond, M ; Chen, TYT ; Javid, N ; Dickinson, JE ; Ives, A ; Hammarberg, K ; Anazodo, A ; Boyle, F ; Fisher, J ; Halliday, L ; Duncombe, G ; McLintock, C ; Wang, AY ; Saunders, C (WILEY, 2022-12)
    OBJECTIVE: To determine the epidemiology, clinical management, and outcomes of women with gestational breast cancer (GBC). METHODS: A population-based prospective cohort study was conducted in Australia and New Zealand between 2013 and 2014 using the Australasian Maternity Outcomes Surveillance System (AMOSS). Women who gave birth with a primary diagnosis of breast cancer during pregnancy were included. Data were collected on demographic and pregnancy factors, GBC diagnosis, obstetric and cancer management, and perinatal outcomes. The main outcome measures were preterm birth, maternal complications, breastfeeding, and death. RESULTS: Forty women with GBC (incidence 7.5/100 000 women giving birth) gave birth to 40 live-born babies. Thirty-three (82.5%) women had breast symptoms at diagnosis. Of 27 women diagnosed before 30 weeks' gestation, 85% had breast surgery and 67% had systemic therapy during pregnancy. In contrast, all 13 women diagnosed from 30 weeks had their cancer management delayed until postdelivery. There were 17 preterm deliveries; 15 were planned. Postpartum complications included the following: hemorrhage (n = 4), laparotomy (n = 1), and thrombocytopenia (n = 1). There was one late maternal death. Eighteen (45.0%) women initiated breastfeeding, including 12 of 23 women who had antenatal breast surgery. There were no perinatal deaths or congenital malformations, but 42.5% of babies were preterm, and 32.5% were admitted for higher-level neonatal care. CONCLUSIONS: Gestational breast cancer diagnosed before 30 weeks' gestation was associated with surgical and systemic cancer care during pregnancy and planned preterm birth. In contrast, cancer treatment was deferred to postdelivery for women diagnosed from 30 weeks, reflecting the complexity of managing expectant mothers with GBC in multidisciplinary care settings.
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    Breast surgery: a narrative review
    Saunders, CM (WILEY, 2022-09-05)
    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.
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    Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery
    Gong, P ; Chin, SL ; Allen, WM ; Ballal, H ; Anstie, JD ; Chin, L ; Ismail, HM ; Zilkens, R ; Lakhiani, DD ; McCarthy, M ; Fang, Q ; Firth, D ; Newman, K ; Thomas, C ; Li, J ; Sanderson, RW ; Foo, KY ; Yeomans, C ; Dessauvagie, BF ; Latham, B ; Saunders, CM ; Kennedy, BF (AMER ASSOC CANCER RESEARCH, 2022-11-01)
    UNLABELLED: Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery. However, current QME methods, in common with most proposed intraoperative solutions, cannot image cancer directly in the patient, making their translation to clinical use challenging. In this proof-of-concept study, we aimed to determine whether a handheld QME probe, designed to interrogate the surgical cavity, can detect residual cancer directly in the breast cavity in vivo during BCS. In a first-in-human study, 21 BCS patients were scanned in vivo with the QME probe by five surgeons. For validation, protocols were developed to coregister in vivo QME with postoperative histopathology of the resected tissue to assess the capability of QME to identify residual cancer. In four cavity aspects presenting cancer and 21 cavity aspects presenting benign tissue, QME detected elevated stiffness in all four cancer cases, in contrast to low stiffness observed in 19 of the 21 benign cases. The results indicate that in vivo QME can identify residual cancer by directly imaging the surgical cavity, potentially providing a reliable intraoperative solution that can enable more complete cancer excision during BCS. SIGNIFICANCE: Optical imaging of microscale tissue stiffness enables the detection of residual breast cancer directly in the surgical cavity during breast-conserving surgery, which could potentially contribute to more complete cancer excision.
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    Multimodal imaging needle combining optical coherence tomography and fluorescence for imaging of live breast cancer cells labeled with a fluorescent analog of tamoxifen
    Scolaro, L ; Lorenser, D ; Quirk, BC ; Kirk, RW ; Ho, LA ; Thomas, E ; Li, J ; Saunders, CM ; Sampson, DD ; Fuller, RO ; McLaughlin, RA (SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS, 2022-07-01)
    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.
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    Streamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial
    Quinn, VF ; Meiser, B ; Kirk, J ; Tucker, KM ; Watts, KJ ; Rahman, B ; Peate, M ; Saunders, C ; Geelhoed, E ; Gleeson, M ; Barlow-Stewart, K ; Field, M ; Harris, M ; Antill, YC ; Cicciarelli, L ; Crowe, K ; Bowen, MT ; Mitchell, G (NATURE PUBLISHING GROUP, 2017-04)
    PURPOSE: Increasingly, women newly diagnosed with breast cancer are being offered treatment-focused genetic testing (TFGT). As the demand for TFGT increases, streamlined methods of genetic education are needed. METHODS: In this noninferiority trial, women aged <50 years with either a strong family history (FH+) or other features suggestive of a germ-line mutation (FH-) were randomized before definitive breast cancer surgery to receive TFGT education either as brief written materials (intervention group (IG)) or during a genetic counseling session at a familial cancer clinic (usual-care group (UCG)). Women completed self-report questionnaires at four time points over 12 months. RESULTS: A total of 135 women were included in the analysis, all of whom opted for TFGT. Decisional conflict about TFGT choice (primary outcome) was not inferior in the IG compared with the UCG (noninferiority margin of -10; mean difference = 2.45; 95% confidence interval -2.87-7.76; P = 0.36). Costs per woman counseled in the IG were significantly lower (AUD$89) compared with the UCG (AUD$173; t(115) = 6.02; P < 0.001). CONCLUSION: A streamlined model of educating women newly diagnosed with breast cancer about TFGT seems to be a cost-effective way of delivering education while ensuring that women feel informed and supported in their decision making, thus freeing resources for other women to access TFGT.Genet Med 19 4, 448-456.
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    Multi-class classification of breast tissue using optical coherence tomography and attenuation imaging combined via deep learning
    Foo, KY ; Newman, K ; Fang, Q ; Gong, P ; Ismail, HM ; Lakhiani, DD ; Zilkens, R ; Dessauvagie, BF ; Latham, B ; Saunders, CM ; Chin, L ; Kennedy, BF (Optica Publishing Group, 2022-06-01)
    We demonstrate a convolutional neural network (CNN) for multi-class breast tissue classification as adipose tissue, benign dense tissue, or malignant tissue, using multi-channel optical coherence tomography (OCT) and attenuation images, and a novel Matthews correlation coefficient (MCC)-based loss function that correlates more strongly with performance metrics than the commonly used cross-entropy loss. We hypothesized that using multi-channel images would increase tumor detection performance compared to using OCT alone. 5,804 images from 29 patients were used to fine-tune a pre-trained ResNet-18 network. Adding attenuation images to OCT images yields statistically significant improvements in several performance metrics, including benign dense tissue sensitivity (68.0% versus 59.6%), malignant tissue positive predictive value (PPV) (79.4% versus 75.5%), and total accuracy (85.4% versus 83.3%), indicating that the additional contrast from attenuation imaging is most beneficial for distinguishing between benign dense tissue and malignant tissue.
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    Optical palpation for tumor margin assessment in breast-conserving surgery
    Foo, KY ; Kennedy, KM ; Zilkens, R ; Allen, WM ; Fang, Q ; Sanderson, RW ; Anstie, J ; Dessauvagie, BF ; Latham, B ; Saunders, CM ; Chin, L ; Kennedy, BF (OPTICAL SOC AMER, 2021-03-01)
    Intraoperative margin assessment is needed to reduce the re-excision rate of breast-conserving surgery. One possibility is optical palpation, a tactile imaging technique that maps stress (force applied across the tissue surface) as an indicator of tissue stiffness. Images (optical palpograms) are generated by compressing a transparent silicone layer on the tissue and measuring the layer deformation using optical coherence tomography (OCT). This paper reports, for the first time, the diagnostic accuracy of optical palpation in identifying tumor within 1 mm of the excised specimen boundary using an automated classifier. Optical palpograms from 154 regions of interest (ROIs) from 71 excised tumor specimens were obtained. An automated classifier was constructed to predict the ROI margin status by first choosing a circle diameter, then searching for a location within the ROI where the circle was ≥ 75% filled with high stress (indicating a positive margin). A range of circle diameters and stress thresholds, as well as the impact of filtering out non-dense tissue regions, were tested. Sensitivity and specificity were calculated by comparing the automated classifier results with the true margin status, determined from co-registered histology. 83.3% sensitivity and 86.2% specificity were achieved, compared to 69.0% sensitivity and 79.0% specificity obtained with OCT alone on the same dataset using human readers. Representative optical palpograms show that positive margins containing a range of cancer types tend to exhibit higher stress compared to negative margins. These results demonstrate the potential of optical palpation for margin assessment.