Abstract Aim To evaluate trends in the risk of local recurrences after breast-conserving treatment (BCT) and to examine the impact of local recurrence (LR) on distant relapse-free survival in a ...large, population-based cohort of women aged ⩽40 years with early-stage breast cancer. Methods All women ( n = 1143) aged ⩽40 years with early-stage (pT1-2/cT1-2, N0-2, M0) breast cancer who underwent BCT in the south of the Netherlands between 1988 and 2010 were included. BCT consisted of local excision of the tumour followed by irradiation of the breast. Results After a median follow-up of 8.5 (0.1–24.6) years, 176 patients had developed an isolated LR. The 5-year LR-rate for the subgroups treated in the periods 1988–1998, 1999–2005 and 2006–2010 were 9.8% (95% confidence interval (CI) 7.1–12.5), 5.9% (95% CI 3.2–8.6) and 3.3% (95% CI 0.6–6.0), respectively ( p = 0.006). In a multivariate analysis, adjuvant systemic treatment was associated with a reduced risk of LR of almost 60% (hazard ratio (HR) 0.42; 95% CI 0.28–0.60; p < 0.0001). Patients who experienced an early isolated LR (⩽5 years after BCT) had a worse distant relapse-free survival compared to patients without an early LR (HR 1.83; 95% CI 1.27–2.64; p = 0.001). Late local recurrences did not negatively affect distant relapse-free survival (HR 1.24; 95% CI 0.74–2.08; p = 0.407). Conclusion Local control after BCT improved significantly over time and appeared to be closely related to the increased use and effectiveness of systemic therapy. These recent results underline the safety of BCT for young women with early-stage breast cancer.
The existence of multiple independently derived populations in landlocked marine lakes provides an opportunity for fundamental research into the role of isolation in population divergence and ...speciation in marine taxa. Marine lakes are landlocked water bodies that maintain a marine character through narrow submarine connections to the sea and could be regarded as the marine equivalents of terrestrial islands. The sponge Suberites diversicolor (Porifera: Demospongiae: Suberitidae) is typical of marine lake habitats in the Indo-Australian Archipelago. Four molecular markers (two mitochondrial and two nuclear) were employed to study genetic structure of populations within and between marine lakes in Indonesia and three coastal locations in Indonesia, Singapore and Australia. Within populations of S. diversicolor two strongly divergent lineages (A & B) (COI: p = 0.4% and ITS: p = 7.3%) were found, that may constitute cryptic species. Lineage A only occurred in Kakaban lake (East Kalimantan), while lineage B was present in all sampled populations. Within lineage B, we found low levels of genetic diversity in lakes, though there was spatial genetic population structuring. The Australian population is genetically differentiated from the Indonesian populations. Within Indonesia we did not record an East-West barrier, which has frequently been reported for other marine invertebrates. Kakaban lake is the largest and most isolated marine lake in Indonesia and contains the highest genetic diversity with genetic variants not observed elsewhere. Kakaban lake may be an area where multiple putative refugia populations have come into secondary contact, resulting in high levels of genetic diversity and a high number of endemic species.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Full-field digital mammography (FFDM) has replaced screen-film mammography (SFM) in most breast screening programs. We analyzed the impact of this replacement on the screening outcome.
The study ...population consisted of a consecutive series of 60 770 analog and 63 182 digital screens. During a 1-year follow-up, we collected breast imaging reports, biopsy results and surgical reports of all the referred women.
The referral rate and the cancer detection rate at FFDM were, respectively, 3.0% and 6,6‰, compared with 1.5% (P < 0.001) and 4.9‰ (P < 0.001) at SFM. Positive predictive values of referral and percutaneous biopsies were lower at FFDM, respectively, 21.9% versus 31.6% (P < 0.001) and 42.9% versus 62.8% (P < 0.001). Per 1000 screened women, there was a significant increase with FFDM versus SFM in the detection rate of low- and intermediate-grade ductal carcinoma in situ (DCIS) (+0.7), invasive T1a-c cancers (+0.9), invasive ductal cancers (+0.9), low-grade (+1.1), node-negative invasive cancers (+1.2), estrogen-receptor or progesterone-receptor-positive invasive cancers (respectively, +0.9 and +1.1) and Her2/Neu-negative (+0.8) invasive cancers. Mastectomy rates were stable at 1.1 per 1,000 screens.
FFDM significantly increased the referral rate and cancer detection rate, at the expense of a lower positive predictive value of referral and biopsy. Extra tumors detected at FFDM were mostly low-intermediate grade DCIS and smaller invasive tumors, of more favorable tumor characteristics. Mastectomy rates were not increased in the FFDM population, while increased over-diagnosis cannot be excluded.
Risk factors for local and distant recurrence after breast-conserving therapy and mastectomy were compared to define guidelines for the decision making between both treatments.
The data of two ...randomized clinical trials for stage I and II breast cancer patients were pooled. The total number of patients in the study was 1,772, of whom 879 underwent breast conservation, and 893, modified radical mastectomy. Representative slides of the primary tumor were available for histopathologic review in 1,610 cases (91%).
There were 79 patients with local recurrence after breast-conservation and 80 after mastectomy, the 10-year rates being 10% (95% confidence interval CI, 8% to 13%) and 9% (95% CI, 7% to 12%), respectively. Age no more than 35 years (compared with age >60: hazard ratio HR, 9.24; 95% CI, 3.74 to 22.81) and an extensive intraductal component (HR, 2.52; 95% CI, 1.26 to 5.00) were significantly associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion was predictive of the risk of local recurrence, irrespective of the type of primary treatment (P <.01). Tumor size, nodal status, high histologic grade, and vascular invasion were all highly significant predictors of distant disease after breast-conserving therapy and mastectomy (P <.01). Age no more than 35 years and microscopic involvement of the excision margin were additional independent predictors of distant disease after breast-conserving therapy (P <.01).
Age no more than 35 years and the presence of an extensive intraductal component are associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion causes a higher risk of local recurrence after mastectomy as well as after breast-conserving therapy and should therefore not be used for deciding between the two treatments.
Abstract Objective Recent studies indicate that removal of the primary tumour may have a beneficial effect on mortality risk of patients with primary distant metastatic breast cancer (stage IV), ...although most of them did not rule out confounding by the presence of co-morbidity. In this retrospective study the impact of surgical resection of the primary tumour on the survival of patients with primary distant metastatic disease is investigated, taking into account the presence of co-morbidity and other potential confounders. Methods Between 1993 and 2004, 15 769 patients with breast cancer were diagnosed in the south of the Netherlands. This study included the 728 patients with distant metastatic disease at initial presentation, which was 5% of all patients. Of them, 40% had surgery of the primary tumour. Follow-up was carried out until 1 July 2006. Results Median survival of the patients who had surgery of their primary tumour was significantly longer than for the patients who did not have surgery (31 vs. 14 months). The 5-year survival rates were 24.5% and 13.1%, respectively ( p < 0.0001). In a multivariable Cox regression analysis, adjusting for age, period of diagnosis, T-classification, number of metastatic sites, co-morbidity, use of loco-regional radiotherapy and use of systemic therapy, surgery appeared to be an independent prognostic factor for overall survival (HR = 0.62; 95% CI 0.51–0.76). Conclusion Removal of the primary tumour in patients with primary distant metastatic disease was associated with a reduction of the mortality risk of around 40%. The association was independent of age, presence of co-morbidity and other potential confounders, but a randomized controlled trial will be needed to rule out residual confounding.
The giant barrel sponge Xestospongiatestudinaria is an ecologically important species that is widely distributed across the Indo-Pacific. Little is known, however, about the precise biogeographic ...distribution and the amount of morphological and genetic variation in this species. Here we provide the first detailed, fine-scaled (<200 km(2)) study of the morphological and genetic composition of X. testudinaria around Lembeh Island, Indonesia. Two mitochondrial (CO1 and ATP6 genes) and one nuclear (ATP synthase β intron) DNA markers were used to assess genetic variation. We identified four distinct morphotypes of X. testudinaria around Lembeh Island. These morphotypes were genetically differentiated with both mitochondrial and nuclear markers. Our results indicate that giant barrel sponges around Lembeh Island, which were all morphologically identified as X. testudinaria, consist of at least two different lineages that appear to be reproductively isolated. The first lineage is represented by individuals with a digitate surface area, CO1 haplotype C5, and is most abundant around the harbor area of Bitung city. The second lineage is represented by individuals with a predominantly smooth surface area, CO1 haplotype C1 and can be found all around Lembeh Island, though to a lesser extent around the harbor of Bitung city. Our findings of two additional unique genetic lineages suggests the presence of an even broader species complex possibly containing more than two reproductively isolated species. The existence of X. testudinaria as a species complex is a surprising result given the size, abundance and conspicuousness of the sponge.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The prevalence of coexistent diseases in addition to breast cancer becomes increasingly important in an ageing population. However, the clinical implications are unclear. The age-specific prevalence ...of serious comorbidity among all new breast cancer patients diagnosed from 1995 to 2001 (
n
=
8966) in the South of the Netherlands was analysed in relation to age, stage and treatment. Independent prognostic effects of age and comorbidity were evaluated (follow-up was continued until 1 January 2004). The prevalence of comorbidity increased from 9% for those aged <50 years to 56% for patients aged 80+ years. The most frequent conditions were cardiovascular disease (7%), diabetes mellitus (7%), and previous cancer (6%). In the presence of comorbidity, fewer patients received radiotherapy (51% vs. 66%,
P
<
0.0001) and fewer patients who underwent breast-conserving surgery also had axillary dissection (
P
<
0.0001). Relative 5-year survival rates for patients without comorbidity (87%) were significantly higher (
P
<
0.01) than those for patients with previous cancer (77%), diabetes mellitus (78%), and for patients with 2+ coexistent diseases (59%). Relative survival of patients without comorbidity increased with age to 93% for patients older than 70 years. Comorbidity negatively affected prognosis, independent of age, stage of disease, and treatment (Hazard Ratio (HR)
=
1.3,
P
=
0.0001 for one coexistent disease and HR
=
1.4,
P
=
0.0001 for 2+ coexistent diseases). The most important effects were found for previous cancer (HR
=
1.4,
P
=
0.003), cerebrovascular disease (HR
=
1.6,
P
<
0.004) or dementia (HR
=
2.3,
P
<
0.0001). Elderly breast cancer patients can be divided in those without other diseases, who have a relatively good prognosis, and those who have at least one other serious coexistent disease and significantly poorer prognosis.
Abstract Introduction We retrospectively investigated the possible influence of a simultaneous integrated boost (SIB), hypofractionation and oncoplastic surgery on cosmetic outcome in 125 patients ...with stage I–II breast cancer treated with breast conserving therapy (BCT). Patients and methods The boost was given sequentially (55%) or by SIB (45%); fractionation was conventional (83%) or hypofractionated (17%); the surgical technique was a conventional lumpectomy (74%) or an oncoplastic technique (26%). We compared cosmetic results subjectively using a questionnaire independently completed by the patient and by the physician and objectively with the BCCT.core software. Independent-samples T-tests were used to compare outcome in different groups. Patients also completed the EORTC QLQ C30 and BR23. Results Univariate analyses indicated no significant differences of the cosmetic results (P ≤ 0.05) for the type of boost or fractionation. However, the conventional lumpectomy group scored significantly better than the oncoplastic group in the BCCT.core evaluation, without a significant difference in the subjective cosmetic evaluation. Quality of life outcome was in favour of SIB, hypofractionation and conventional surgery. Conclusion Our study indicates that the current RT techniques seem to be safe for cosmetic outcome and quality of life. Further investigation is needed to verify the possible negative influence of oncoplastic surgery on the cosmetic outcome and the quality of life as this technique is especially indicated for patients with an unfavourable tumour/breast volume ratio.
On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology.
Women with ...primary nonmetastatic invasive ductal or (mixed type) lobular breast cancer, aged 50–70 years, diagnosed between 1995 and 2008, were selected from the Netherlands Cancer Registry and followed until January 1, 2010. The patients were divided in two groups: one group receiving adjuvant hormonal therapy only and the other receiving adjuvant hormonal therapy in combination with adjuvant chemotherapy.
In total, 19 609 patients had ductal cancer and 3685 had lobular cancer. The 10-year overall survival rate in ductal cancer when treated with hormonal therapy alone was 69%, compared with 74% with the combination therapy (P < 0.0001). In lobular cancer, 10-year survival rates were 68% after hormonal treatment alone and 66% after the combination therapy (P = 0.45). The hazard ratio (HR) for mortality in ductal cancer after combination therapy was 0.70 95% confidence interval (CI) 0.64–0.76; P < 0.0001, compared with hormonal treatment alone. The HR in lobular cancer was 1.00 (95% CI 0.82–1.21; P = 0.97).
Adjuvant chemotherapy seems to confer no additional beneficial effects in postmenopausal patients with pure or mixed type lobular breast cancer receiving hormonal therapy.