Phase-referenced Interferometry and Narrow-angle Astrometry with SUSI

This thesis describes the development of an astrometric facility at the Sydney University Stellar Interferometer (SUSI) with an aim to measure at high precision the relative astrometry of bright close binary stars and ultimately to detect the presence of exoplanets within those binary star systems through observations of the systems’ perturbed motion. At the core of the facility is a new beam combiner that is phase-referenced to an existing primary beam combiner in the visible wave- length regime. The latter provides post-processed fringe-tracking information to the former for fringe stabilization and coherent integration of pre-recorded stellar fringes using newly developed data reduction software. Interference fringe packets of a binary star are recorded alternately; first the fringe packet of the primary, then the secondary, finally back to the primary again. The measurement of the fringe packet separation is facilitated by an air-filled differential delay line and a network of interferometer-based metrology systems. Characterizations and initial astronomical observations carried out with the dual beam combiner setup demonstrated for the first time the success of the dual-star phase-referencing technique in visible (~1μm) wavelengths. The current astrometric precision is larger than 100μas while the long term astrometric accuracy is yet to be characterized. In a parallel development, a complementary observing method using only the primary beam combiner is also demonstrated in this thesis. Relative astrometry of binary stars up to ~0.8” separation with this technique has been demonstrated to have precision of better than 100μas. A simple detection limit analysis based on a list of target binary stars estimates up to two exoplanet detections can be achieved with SUSI if the new astrometric facility attains precision of 10μas while the primary beam combiner operates at its designed peak performance. Finally, one new stellar companion was resolved and a preliminary astrometry for another suspected companion was estimated from the astronomical observation data collected throughout the course of this thesis

Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition.

Contains fulltext : 58587.pdf (publisher's version ) (Open Access)BACKGROUND: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women. METHODS: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups. RESULTS: We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups. CONCLUSIONS: MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer

Hereditary breast cancer growth rates and its impact on screening policy

Contains fulltext : 47763.pdf (publisher's version ) (Closed access)Imaging is often performed yearly for the surveillance of BRCA1/2 mutation carriers and women at high familial breast cancer risk. Growth of cancers in carriers may be faster as these tumours are predominantly high grade. Quantitative data on tumour growth rates in these 2 groups are lacking. Here, we have examined 80 high-risk women under surveillance for tumour size at diagnosis and preceding examinations at mammography and/or MRI. Tumour volume doubling time (DT) was assessed in 30 cancers in BRCA1/2 mutation carriers and 25 non-carriers. Impact of age and menopausal status were also evaluated. Mean DT of all invasive cancers was shorter in carriers (45 days CI: 26-73) than non-carriers (84 days CI: 58-131) (P = 0.048). Mean age at diagnosis was lower in carriers (40 years) than non-carriers (45 years) (P = 0.007). At multivariable analysis only age (P = 0.03), not risk-group (P = 0.26) nor menopause (P = 0.58) correlated significantly with DT. The mean growth rate slowed down to half in each successive 10 years-older group. In conclusion, age at detection indicated the growth rates of hereditary and familial breast cancers. It is recommended that the screening frequency should be adjusted according to a woman's age and a high-sensitive biannual test may be appropriate before the age of 40 years

BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study.

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Relevance and efficacy of breast cancer screening in BRCA1 and BRCA2 mutation carriers above 60 years: a national cohort study

Item does not contain fulltextAnnual MRI and mammography is recommended for BRCA1/2 mutation carriers to reduce breast cancer mortality. Less intensive screening is advised >/=60 years, although effectiveness is unknown. We identified BRCA1/2 mutation carriers without bilateral mastectomy before age 60 to determine for whom screening >/=60 is relevant, in the Rotterdam Family Cancer Clinic and HEBON: a nationwide prospective cohort study. Furthermore, we compared tumour stage at breast cancer diagnosis between different screening strategies in BRCA1/2 mutation carriers >/=60. Tumours >2 cm, positive lymph nodes, or distant metastases at detection were defined as "unfavourable." Of 548 BRCA1/2 mutation carriers >/=60 years in 2012, 395 (72%) did not have bilateral mastectomy before the age of 60. Of these 395, 224 (57%) had a history of breast or other invasive carcinoma. In 136 BRCA1/2 mutation carriers, we compared 148 breast cancers (including interval cancers) detected >/=60, of which 84 (57%) were first breast cancers. With biennial mammography 53% (30/57) of carcinomas were detected in unfavourable stage, compared to 21% (12/56) with annual mammography (adjusted odds ratio: 4.07, 95% confidence interval [1.79-9.28], p = 0.001). With biennial screening 40% of breast cancers were interval cancers, compared to 20% with annual screening (p = 0.016). Results remained significant for BRCA1 and BRCA2 mutation carriers, and first breast cancers separately. Over 70% of 60-year old BRCA1/2 mutation carriers remain at risk for breast cancer, of which half has prior cancers. When life expectancy is good, continuation of annual breast cancer screening of BRCA1/2 mutation carriers >/=60 is worthwhile

Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer.

Contains fulltext : 52475.pdf (publisher's version ) (Closed access