Asynchronous Bilateral Breast Research Articles

The usefulness of ultrasonography in a ductal carcinoma in situ screening program for Japanese woman.

24 Background: Although varying among areas, the mammogram (MMG) screening rate is very low in Japan as compared to the U.S. at approximately 20% versus nearly 80% in the U.S. On the other hand, rates of ductal carcinoma in situ (DCIS) detection among diagnosed breast cancers differ minimally: 20% in the U.S., and 15% in Japan. This is a small difference considering the difference MMG screening rates. Racial differences have been suggested to be attributable to the organization of screening programs in Japan, which also use ultrasonography (US) breast cancer screening, as well as breast size in Japanese women. Methods: We retrospectively evaluated MMG and US images of 91 DCIS cases, all 91 Japanese women who under underwent surgery between May 2010 and February 2012. US (TOSHIBA Aplio, probe 9MHz) was performed with knowledge of MMG findings. The 91 cases were divided into group with tumor detected by MMG and US (M&U), MMG detection only (M), and US detection only (U). The following parameters were analyzed: US shape (Tumor-forming lesion: TFL, Non-tumor-forming lesion: NTFL, Cystic-forming lesion: CFL), Skin-Muscle distance: SMD. We excluded asynchronous bilateral breast cancers and micro-invasive DCIS. Results: Sixty-eight lesions (73.0%) were identified by US, which revealed a NTLF in 52 cases, TLF in 9 cases and CFL in 7 cases. All cases with false-negative findings on US (Group M, n = 23) showed micro-calcifications on MMG (n=22) and with the tumor (n=1). In the U group, SMD was only 23 mm versus 43.4mm in the M group. No difference was observed in body mass index or pathological tumor diameter between the U and M. Conclusions: We found US to reveal DCIS in 73% of our cases upon reevaluation. Although US examination would not likely increase the screening detection rate for DCIS in Japanese women, US may reveal more DCIS in Japanese women, in which the breasts are comparatively small, than in western women. Further comparison of possible racial difference is warranted.

Durable tumour responses following primary high dose induction with mistletoe extracts: Two case reports

IntroductionViscum album L. extracts (VAEs) are widely used in the complementary treatment of cancer, to improve quality of life of cancer patients, commonly using subcutaneous application of low doses of VAEs. Case presentationsTwo patients were treated with VAE (AbnobaViscum®) alone, using a combination of intratumoural, subcutaneous and in one case intravenous administration. A 75-year-old lady with relapsed Merkel cell cancer – a rare and aggressive neuro-endocrine cancer of the skin – declined radiotherapy, and was treated with VAE alone over 9.8 months, using a total of 5.8G VAE, averaging 592mg/VAE/month (>300,000ng mistletoe lectin (ML)/month; >2300μg viscotoxin (VTX)/month); the 3cm tumour was impalpable after 4 months and she continues to be in complete remission after 3 years. A 50-year-old postmenopausal woman with asynchronous bilateral breast cancer (right breast: grade 1, hormone sensitive; left breast: grade 3, hormone insensitive and HER2-positive ductal carcinoma), declined all conventional cancer treatment. She was treated with VAE alone for 2.6 years, with a total of 8.9G VAE, averaging 290mg/month (>150,000ngML/month; >1200μgVTX/month); she had complete responses of both tumours after 31 months of intratumoural and subcutaneous VAE application, and remains in remission after 4 years. ConclusionsDurable tumour regression occurred in 2 patients following treatment with VAE, used in higher than generally used doses and combining different applications. Both patients had no other established cancer therapies. Further studies are required to define the strategic role of VAE and its different applications, safety and efficacy.

TH-D-BRA-03: Genetic Susceptibility Radiation Exposure and Risk of Second Primary Breast Cancer

Background: Deficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation induces double strand breaks (DSB). Upon activation by DSB-inducing agents ATM (for ataxia-telangiectasia (A-T) mutated) phosphorylates a large number of downstream targets including the products of several known breast cancer susceptibility genes (e.g. BRCA1 BRCA2 Chek2 p53). In this study we examine whether defects in these breast cancer susceptibility factors are associated with radiation-induced induced breast cancers. Methods: The WECARE Study is a case-control study nested within 5 population-based cancer registries in the US and in Denmark. The 708 cases were women with asynchronous bilateral breast cancer (CBC) and the 1399 controls were women with unilateral breast cancer (UBC) individually matched to cases on year of birth race geographic region and date of diagnosis (interval). All participants were interviewed medical records were comprehensively reviewed and full genetic screening was conducted. For women who received radiation therapy (RT) absorbed radiation doses to quadrants of the (CB) were estimated using dosimetry reconstruction. Rate ratios (RR) and 95% confidence intervals were calculated using multivariable-adjusted conditional logistic regression models. Results: The mean dose to the specific quadrant of the CB tumor was 1.1 Gy. Women <40 years of age who received >1.0Gy and with >5 year follow-up had a 3-fold increased risk of CBC (95% CI-1.1–1.8). The RR of CBC associated with carrying a BRCA1/2 mutation was 4.2 (95% CI=2.8–6.1); however among carriers radiation was not associated with risk. Among women carrying rare ATM missense mutations the risk of developing CBC was slightly increased but was significantly elevated among women treated with RT and strongest for mutations selected on their likelihood to disrupt structure. Conclusions: Risk of radiation-associated CBC was inversely related to age at exposure and dose dependent. A subgroup of rare mutations may increase risk of CBC among women with early onset breast cancer treated with RT. However the fraction of CBC attributed to this is quite small suggesting that radiation contributes little to the already high risk of CBC associated with carrying these breast cancer susceptibility factors. Learning Objectives: 1. Understand the role of DSB in CBC 2. Understand the basic study design of the WECARE Study 3. Understand the issues relating to genetic susceptibility and CBC risk

Dose to the Contralateral Breast From Radiotherapy and Risk of Second Primary Breast Cancer in the WECARE Study

To quantify the risk of second primary breast cancer in the contralateral breast (CB) after radiotherapy (RT) for first breast cancer. The study population included participants in the Women's Environmental, Cancer, and Radiation Epidemiology study: 708 cases (women with asynchronous bilateral breast cancer) and 1399 controls (women with unilateral breast cancer) counter-matched on radiation treatment. Participants were <55 years of age at first breast cancer. Absorbed doses to quadrants of the CB were estimated. Rate ratios (RR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted conditional logistic regression models. Across all patients, the mean radiation dose to the specific quadrant of the CB tumor was 1.1 Gy. Women <40 years of age who received >1.0 Gy of absorbed dose to the specific quadrant of the CB had a 2.5-fold greater risk for CB cancer than unexposed women (RR = 2.5, 95% CI 1.4-4.5). No excess risk was observed in women >40 years of age. Women <40 years of age with follow-up periods >5 years had a RR of 3.0 (95% CI 1.1-8.1), and the dose response was significant (excess RR per Gy of 1.0, 95% CI 0.1-3.0). Women <40 years of age who received a radiation dose >1.0 Gy to the CB had an elevated, long-term risk of developing a second primary CB cancer. The risk is inversely related to age at exposure and is dose dependent.

Oral Contraceptives, Postmenopausal Hormones, and Risk of Asynchronous Bilateral Breast Cancer: The WECARE Study Group

To investigate whether oral contraceptive (OC) use and postmenopausal hormones (PMH) are associated with an increased risk of developing asynchronous bilateral breast cancer among women diagnosed with breast cancer younger than 55 years. The WECARE (Women's Environment, Cancer, and Radiation Epidemiology) study is a population-based, multicenter, case-control study of 708 women with asynchronous bilateral breast cancer and 1,395 women with unilateral breast cancer. Risk factor information collected during a telephone interview focused on exposures before and after the first breast cancer diagnosis. Treatment and tumor characteristics were abstracted from medical records. Multivariable conditional logistic regression was used to estimate rate ratios (RR) and 95% CIs. OC use before the first breast cancer diagnosis was not associated with risk of asynchronous bilateral breast cancer (RR = 0.88; 95% CI, 0.67 to 1.16). OC use after breast cancer diagnosis was also not significantly associated with risk (RR = 1.56; 95% CI, 0.71 to 3.45). Risk did not increase with longer duration of use or among women who had begun using OCs at a younger age. No evidence of an increased risk of asynchronous bilateral breast cancer was observed with PMH use before (RR = 1.21; 95% CI, 0.90 to 1.61) or after breast cancer diagnosis (RR = 1.10; 95% CI, 0.67 to 1.77). Neither duration nor type of PMH were associated with risk. Age at and time since first breast cancer diagnosis did not substantially affect these results. This study provides no strong evidence that OC or PMH use increases the risk of a second cancer in the contralateral breast.

Bilateral extensive vascular calcification of the breast associated with coagulative necrosis: a calciphylaxis-like syndrome

A case of asynchronous bilateral breast necrosis in a 40-year-old woman with untreated chronic hypercholesteraemia is described. Mastectomies were performed, and histological examination revealed bilateral breast calciphylaxis characterized by extensive vascular calcification with coagulative necrosis. Breast calciphylaxis is a rare disease clinically characterized by progressive tissular necrosis with secondary cutaneous ulceration and by vascular calcification and thrombosis. However, the nature of the vascular calcification has remained poorly understood up to now, owing to the absence of any precise mineralogical examination. In this case the mineral deposits were analysed for the first time: only hydroxyapatite was found. The etiology is discussed, and the high cholesterol rate of the patient is implicated.

Estrogen and Progesterone Receptor Content in Bilateral Breast Cancer

Estrogen and progesterone receptor content was determined in 34 patients with synchronous and 23 patients with asynchronous bilateral breast cancer. Steroid receptor content was measured quantitatively by DCC method. It was shown that progesterone receptor content could not be predicted, as well as, that steroid receptor content of the second tumor significantly influenced the development of asynchronous bilateral breast cancer. The high discordance rate concerning histologic type between two tumors within synchronous as well as asynchronous biopsies was observed. The obtained results indicate that both synchronous and asynchronous bilateral breast tumors may be considered as biologically different tumors whose both steroid receptor levels should be determined whenever possible.

Steroid receptor content in synchronous and asynchronous bilateral breast cancer

Steroid receptor content in synchronous and asynchronous bilateral breast cancer

Estrogen receptors in bilateral breast cancer.

Estrogen receptor status, tumor histology, and the interval between the development of tumors were assessed in 99 patients with bilateral breast cancer. Tumors were first grouped into those simultaneously detected in both breasts or within 12 months of each other (synchronous bilateral breast cancer, of which there were 64) and second, those detected within more than 12 months of each other (asynchronous bilateral breast cancer, of which there were 35). Nineteen percent of all tumors were lobular carcinomas. Overall, the rate of receptor discordance between the two tumors was not significantly different from that previously reported between biopsies of primary tumor and metastases in patients with unilateral breast cancer. Synchronous receptor-positive tumors occurred significantly more frequently than expected, suggesting that the development of the two tumors was influenced by a common mechanism. In patients with asynchronous bilateral breast cancer there was a significantly longer interval between tumors if both were receptor-positive compared with concordant receptor-negative tumors and tumors with discordant receptor status. There was a significant discordance in the receptor status of asynchronous tumors when the histology also differed, indicating that the tumors in this group were likely to be separate primary tumors.