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PubMed2004

Breast cancer after curative chemotherapy in non-Hodgkin's lymphoma: examination of the role of drug resistance and retrospective comparison to the outcome of de novo breast cancer.

We examined the outcome of patients who developed breast cancer after curative chemotherapy (CHOP) for aggressive non-Hodgkin's lymphoma (NHL) in comparison to the outcome of a retrospectively selected matched-pair group of patients with de novo breast cancer, and evaluated the role of drug resistance-related protein (MDR, MRP, LRP) expression in breast cancer tissue. Twenty-two patients presented with breast cancer (BC) in complete remission after CHOP for NHL. The median age was 62 (49-70) years, each had high/intermediate grade B-cell NHL treated with 6 courses of CHOP, and were in complete remission. These patients were compared to a matched-pair group of de novo BC patients selected from our database over the same time period. Breast cancer tissue was stained by immunohistochemistry for drug resistance proteins LRP, MRP, and MDR. Breast cancer developed after a median of 26 (9-49) months of NHL diagnosis; breast tumor grades 1-2 were seen in 12, and grade 3 in 10 patients; 15 were negative and 7 weakly positive for estrogen and progesterone receptors. Twelve patients were stage IIIA/B, and 10 stage IV and were treated with conventional chemotherapy regimens. All progressed early in liver (n=13), brain (n=9), lung (n=6), bone (n=8), lymph nodes (n=7) and soft tissue (n=5), and received second-line chemotherapy with mitomycin-C + vinblastine or taxanes. The overall survival was 11.8 (6-26) months (p<0.01). Time from NHL to breast cancer development was 19 (14-27) months in patients with positive drug resistance proteins (group A), and 37 (26-56) months in patients with 1 or 2 positive resistance proteins (group B) (p<0.001). In patients with stage IIIA/B disease, there was no difference between the examined and control matched-pair group in median TTP, but there was in overall survival (OS) (23 vs 36 months, p=0.029). In advanced disease, there were more responders in the control vs the examined group (p=0.07). Patients in the control matched-pair group had more prolonged OS when compared to group A patients who developed BC in <24 months from NHL to BC (p=0.017). We conclude that breast cancer developing shortly after a complete response in NHL, is an aggressive disease variant with minimal potential for response to conventional chemotherapy. Analysis of drug resistance mechanisms concerning MDR, MRP and LRP indicates that most of these patients have BC that overexpress these proteins leading to the suggestion that these mechanisms might be a part of the aggressive disease phenotype and partially explain the poor outcome.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Implementing clinical practice guidelines: a community-based audit of breast cancer treatment. Australian Capital Territory and South Eastern New South Wales Breast Cancer Treatment Group.

OBJECTIVE: To improve breast cancer management by facilitating implementation of treatment guidelines. DESIGN: A prospective, longitudinal study (developed by clinicians and consumers) of all patients with newly diagnosed breast cancer. Four locally agreed breast cancer management guidelines were established (based on 1995 National Health and Medical Research Council guidelines) as practice indicators. SETTING: Breast cancer treatment facilities and medical practices in the Australian Capital Territory and South Eastern New South Wales, May 1997 to July 1998. MAIN OUTCOME MEASURES: Actual treatment received by patients for primary breast cancer during the study period. RESULTS: During the 14 months of the study, 19 clinicians registered 221 new patients with a proven diagnosis of breast cancer. Of 191 women with localised invasive breast cancer, 112 (59%) had tumours 2 cm or less in diameter. Axillary surgery in 173 (91%) of these women showed 107 (56%) had no axillary lymph node involvement. Of 87 women treated with breast-conserving surgery for locally invasive cancer, 85 (98%) also received postoperative radiotherapy. Some form of systemic adjuvant therapy was indicated in 99 women (axillary nodes positive or tumours > 2 cm diameter) and this treatment was received by 95 (96%). All 27 women aged under 50 years with node-positive disease received adjuvant chemotherapy. CONCLUSIONS: Enhancing uptake of breast cancer management guidelines is feasible at a regional level with an audit program and broad support among clinicians and consumers.

Adult↗
PubMedDate not supplied

Breast conservation therapy for breast cancer treatment in Brown County.

The Northeast Wisconsin Cancer Registry and a patient survey was utilized to examine the use of breast conservation surgery in Brown County between 1991 and 1997 and the factors influencing patients' treatment decisions. In all patients, the rate of breast conservation rose from approximately 30% to 44% during that time period. The percent of all patients with stage 0, I or II breast cancer who were potential candidates for breast conservation based on their stage rose from 89% in 1991 to 96% in 1997. The percent of Stage I and Stage II patients who underwent breast conserving surgery rose from 29% in 1991 to 38% in 1997. There was a higher use of breast conserving surgery in younger women (approximately 50% in age 35 to 49 years old in 1997) compared to women older than 62 (33% in 1997). Breast conservation surgery was used in 47% of patients with AJCC T1 (primary tumors less than 2 cm) and in 25% of patients with T2 lesions (primary tumors 2 to 5 cm); and more often in node negative than in node positive patients (51% vs. 20%). A patient survey revealed that a majority of patients felt that their surgeon's recommendation was the most important influence in making their surgical decision and that their fear of cancer recurrence most strongly influenced their decision on a personal level. Fewer than half of the women were referred to a medical oncologist, radiation oncologist, plastic surgeon or second opinion surgeon prior to surgery. Breast conservative treatment is increasingly utilized in Northeastern Wisconsin and women depend on their surgeon to give them clear, complete, non-biased information balanced with emotional support during the time when they are asked to make the complex decision of the type of breast cancer surgery they desire.

Adult↗
PubMedDate not supplied

The impact of contralateral breast cancer on the outcome of breast cancer patients treated by mastectomy.

PURPOSE: To evaluate the clinical and pathological features of breast cancer patients who develop contralateral breast cancer (CBC) and assess the impact of the second breast cancer on their prognosis. PATIENTS AND METHODS: This retrospective study includes 2136 women with stage I-III breast cancer treated between 1927 and 1987 at the University of Chicago Hospitals. A total of 132 (6.2%) developed CBC during a median follow-up period of 14.2 years; all of them were treated with mastectomy for both breast cancers. We compare the prognostic characteristics, treatments, and outcomes of patients who developed bilateral breast cancer with those who had only unilateral breast cancer (UBC). We also compare the features of the first and the second tumors among patients with bilateral breast cancer (BBC). RESULTS: The annual incidence rate for CBC remained constant at an average rate of 0.23%, resulting in a cumulative incidence rate of 6.2%. Patients with BBC were significantly younger than those with UBC (median age, 51 years vs 54 years). No other significant differences were observed between BBC and UBC patients. Among BBC patients, the second cancer was smaller (2.0 cm vs 3.0 cm) and was associated with a lower incidence of axillary node involvement (29% vs 52%). The development of CBC was associated with worse survival (hazard ratio = 1.46 in comparison with patients who did not develop CBC, 95% CI of 1.09-1.95). On multivariate analysis, factors that decreased the disease-specific survival (DSS) in patients with BBC were a higher number of positive lymph nodes of the first and second cancers, a larger size of the second cancer, and a shorter interval between the two primaries. DISCUSSION: At the time of diagnosis of first breast cancer, BBC patients were significantly younger than UBC patients. The second cancer among the BBC patients was at an earlier stage than the first one; however, no difference was noticed in the pathological feature between the cancer in the UBC patients and the first cancer of BBC patients. There is an indication that the longer the interval between the two cancers, the better the survival of the BBC patients.

Adult↗
PubMedDate not supplied

The role of technetium-99m methoxyisobutylisonitrile scintimammography in diagnosis of breast cancer in patients with mammographically dense breasts.

The purpose of this study was to assess the contribution of techentium-99m methoxyisobutylisonitrile (Tc-99m sestamibi) scintimammography in the diagnosis of breast cancer in 32 female patients with indeterminate mammographic probability of malignancy because of mammographically dense breasts. All the breast masses were removed and histopathological diagnoses were obtained in all cases. The results showed that scintimammography with Tc-99m sestamibi was positive in 21 patients (20 true-positive, 4 false-positive) and negative in 11 patients (7 true-negative, 4 false-negative). The diagnostic sensitivity, specificity and accuracy rates were 83%, 88% and 84%, respectively, in the differentiation of malignant from benign breast masses in the patients with mammographically dense breasts. The detection of malignant breast tumors by Tc-99m sestamibi scintimammography was independent of the density of the breast tissue. In conclusion, Tc-99m sestamibi scintimammography appears to be a useful diagnostic method for the detection of breast cancer in patients with non-diagnostic mammograms because of mammographically dense breasts.

Adult↗
PubMed2001

Malignant breast epithelial cells stimulate aromatase expression via promoter II in human adipose fibroblasts: an epithelial-stromal interaction in breast tumors mediated by CCAAT/enhancer binding protein beta.

Expression of aromatase P450 (P450arom), which catalyzes the formation of estrogens, is aberrantly increased in adipose fibroblasts surrounding breast carcinomas, giving rise to proliferation of malignant cells. Aromatase in human adipose tissue is primarily expressed in undifferentiated fibroblasts under the control of several distinct and alternatively used P450arom promoters. In tumor-free breast adipose tissue, P450arom is usually expressed at low levels via a distal promoter (I.4), whereas in the breast adipose tissue bearing a tumor, P450arom is increased through the activation of two proximal promoters, II and I.3. Because the in vivo activation of P450arom promoter II is a key event responsible for aberrantly high P450arom expression in breast tumors, we studied the molecular basis for the enhancement of P450arom promoter II using human adipose fibroblasts (HAFs) in primary culture treated with T47D breast cancer cell-conditioned medium (TCM) as a model system. Upon treatment with TCM, HAFs displayed a striking induction of P450arom mRNA levels via promoter II usage. This effect appeared to be specific for malignant breast epithelial cells, because conditioned media from breast cancer cell lines T47D and MCF-7 induced promoter II activity, whereas normal breast epithelial cells or liver or prostate cancer cell lines did not produce such an effect. Although treatment with a cyclic AMP analogue also caused a switch in the promoter use from I.4 to II in cultured HAFs, TCM-induced promoter II use was found to be mediated via a cyclic AMP-independent pathway. Use of serial deletion mutants of the promoter II 5'-flanking sequence revealed the presence of critical cis-acting elements in the -517/-278 bp region, which regulate the baseline activity. TCM caused a 5.7-fold induction of the -517-bp promoter II construct, whereas site-directed mutagenesis of a CCAAT/enhancer binding protein (C/EBP) binding site (-317/-304 bp) abolished both baseline and TCM-induced activities. Ectopic expressions of C/EBPalpha and C/EBPbeta, but not C/EBPdelta, significantly induced promoter II activity. Moreover, we demonstrated the presence of both C/EBPbeta and C/EBPdelta but not C/EBPalpha in a DNA-protein complex formed by the nuclear extract from TCM-treated HAFs and a probe containing this critical C/EBP binding element (-317/-304 bp). Finally, treatment of HAFs with TCM strikingly induced C/EBPbeta expression, whereas this did not affect the levels of C/EBPalpha or C/EBPdelta transcripts. In conclusion, malignant breast epithelial cells secrete factors, which induce aromatase expression in adipose fibroblasts via promoter II. This is, at least in part, mediated by a TCM-induced up-regulation and enhanced binding of C/EBPbeta to a promoter II regulatory element.

Adipose Tissue↗
PubMed2001

Comparisons of two breast cancer risk estimates in women with a family history of breast cancer.

There is an increasing need for accurate prediction methods of assessing individual risk for breast cancer for both clinical and research purposes. The purpose of this study is to compare the Gail and Claus model risk estimates of breast cancer among women with a family history of breast cancer. This study presents risk estimates from two models of breast cancer risk in 491 women 18 to 74 years of age with a family history of breast cancer who were recruited to risk counseling clinical trials in Seattle, Washington between 1996 and 1997. These trials included women from the general population and additional samples of Ashkenazi Jewish, African-American, and lesbian women. We estimated and compared lifetime (to age 79) and 5-year risk for developing breast cancer using the National Surgical Adjuvant Breast and Bowel Project adaptation of the Gail model and the Claus model. About one-quarter of participants fell into the Gail "high" risk category (> or =1.7% risk of developing breast cancer in the next 5 years). The average lifetime risk was estimated at 13.2% by the Gail model and 11.2% by the Claus model. Estimates from the two models were moderately and positively correlated (r = 0.55) with the Gail model yielding a higher estimate than the Claus model for most participants. If women with a family history of breast cancer are being counseled regarding decisions on genetic testing, tamoxifen use, or other preventive measures, presenting both Claus and Gail estimates may be the best option.

Adolescent↗
PubMed2001

Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells.

Glypicans are a family of glycosylphosphatidylinositol-anchored cell surface heparan sulfate proteoglycans implicated in the control of cellular growth and differentiation. Here we show that glypican-1 is strongly expressed in human breast cancers, whereas expression of glypican-1 is low in normal breast tissues. In contrast, the expression of glypican-3 and -4 is only slightly increased in breast cancers by comparison with normal breast tissues, and glypican-2 and -5 are below the level of detection by Northern blotting in both normal and cancer samples. Treatment of MDA-MB-231 and MDA-MB-468 breast cancer cells with phosphoinositide-specific phospholipase-C abrogated the mitogenic response to two heparin-binding growth factors, heparin-binding epidermal growth factor-like growth factor and fibroblast growth factor 2. Stable transfection of these cells with a glypican-1 antisense construct markedly decreased glypican-1 protein levels and the mitogenic response to the same heparin-binding growth factors, as well as that to heregulin alpha, heregulin beta, and hepatocyte growth factor. Syndecan-1 was also expressed at high levels in both breast cancer tissues and breast cancer cells when compared with normal breast tissues. There was a good correlation between glypican-1 and syndecan-1 expression in the tumors. However, clones expressing the glypican-1 antisense construct did not exhibit decreased syndecan-1 levels, indicating that loss of responsiveness to heparin-binding growth factors in these clones was not due to altered syndecan-1 expression. Furthermore, 8 of 10 tumors with stage 2 or 3 disease exhibited high levels of glypican-1 by Northern blot analysis. In contrast, low levels of glypican-1 mRNA were evident in 1 of 10 tumors with stage 2 or 3 disease and in 9 of 10 tumors with stage 1 disease. Taken together, these data suggest that glypican-1 may play a pivotal role in the ability of breast cancer cells to exhibit a mitogenic response to multiple heparin-binding growth factors and may contribute to disease progression in this malignancy.

Adult↗
PubMed2001

Follow-up of the breast cancer prevention trial and the future of breast cancer prevention efforts.

Women who are at increased risk for developing breast cancer can be identified using quantitative risk assessment models that provide valid estimates of risk. The Breast Cancer Prevention Trial (BCPT, P-1) demonstrated that tamoxifen can reduce the incidence of both invasive and noninvasive breast cancer as well as of bone fractures in women at increased risk. These benefits accrue at the expense of increased risk of endometrial cancer, thromboses, cataracts, and possibly diminished quality of life in postmenopausal women. All premenopausal women with a 5-year risk of developing invasive breast cancer greater than 1.67% derive net benefit from using tamoxifen to reduce the risk. Subset analyses of older postmenopausal women taking raloxifene for the treatment of osteoporosis indicate reduction of breast cancer incidence by more than 70%. These findings led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to design and launch the STAR trial (P-2, the Study of Tamoxifen and Raloxifene). Eligible women are at least 35 years of age and postmenopausal, and they must have either lobular carcinoma in situ (LCIS) or a 5-year risk of invasive breast cancer of at least 1.67% as determined by the Gail model [M. H. Gail et al., J. Natl. Cancer Inst. (Bethesda), 81: 1879-1886, 1989]. Subjects are randomly assigned to receive either tamoxifen 20 mg or raloxifene 60 mg daily in a double-blind, double-dummy design. The trial is designed to recruit a total of 22,000 postmenopausal women and is powered to demonstrate superior efficacy of either agent or their equivalence in reducing the incidence of primary breast cancer. Additional end points will include the incidence of cardiovascular events and bone fractures. Thromboembolic events and endometrial cancer are the predicted toxicities. Ancillary studies of cognitive function will also be performed. Raloxifene should not be used for the reduction of breast cancer risk outside the context of the STAR trial.

Aged↗
PubMed2002

[Clear-cut beneficial effect of breast cancer screening on the trend in breast-conserving surgery].

Since the introduction of mammographic screening, controversies have emerged concerning its effect on mortality as well as on the management of breast cancer. A Dutch population-based study demonstrates a significant difference between screening-detected breast cancers and non-screening-detected breast cancers in terms of smaller tumour size, more favourable nodal status and a 14% increase (difference between percentages) in breast-conserving surgery in favour of the screening-detected group. However, since no overall increase in the rate of breast-conserving therapy was found, the authors concluded that the impact of screening on surgical management was limited. An alternative explanation is that during the 1990s, the indications for breast-conserving surgery have become more restrictive in terms of tumour-free margins. Other investigators have demonstrated similar increases in the rate of breast-conserving surgery in screening-detected breast cancer patients. Although the debate on mammographic screening has definitely not reached its conclusion, Swedish data available clearly demonstrate a decrease in breast cancer mortality (21%) due to mammographic screening, which is contrary to recent criticism.

Breast Neoplasms↗
PubMedDate not supplied

Breast-conserving surgery following radiation therapy of 50 Gy in stages I and II carcinoma of the breast: the experience at one institute in Japan.

This study evaluated the results of breast-conserving therapy experienced in one institute. A total of 217 breasts in 215 patients with clinical stages I and II breast cancer undergoing breast-conserving therapy between August 1991 and December 1999 were included. The actuarial 5-year local recurrence-free survival, disease-free survival and overall survival rates were 97.4%, 88.5% and 92.5%, respectively. Microscopic margins were negative in 176 (81.1%) of the total breasts and positive in 41 (18.9%). There were no differences in the age at operation, tumor size, clinical stage, lymph node status, estrogen receptor status, or distance from tumor to nipple between patients with positive surgical margins and with negative surgical margins. During the follow-up period, local recurrence occurred in seven patients. Local recurrence was significantly less frequent in patients with surgical margin-negative tumors than those with surgical margin-positive tumors, and also in ER-positive tumors than ER-negative or ER-unknown tumors. There was no difference in overall survival between patients with and without breast-recurrence. Using multivariate analysis, the surgical margin was determined to be an independent predictive factor for local recurrence in the conserved breast. Nodal status and ER status were independent prognostic factors, but local recurrence did not have an independent negative impact on survival. We conclude that microscopic surgical margin is the most important factor associated with local recurrence in the conserved breast among patients treated with breast-conserving surgery and radiation therapy of 50 Gy. Local recurrence however, has no adverse effect on survival of patients.

Adult↗
PubMed2003

Aging of stromal-derived human breast fibroblasts might contribute to breast cancer progression.

Age is an important factor in the development and spread of breast cancer. Stromal cells also contribute to breast cancer growth and metastasis through the production of extracellular matrix (ECM) modifiers such as urokinase type plasminogen activator (uPA), its receptor (uPAR), its inhibitors (PAI-1 and PAI-2), matrix metalloproteinases (MMPs), and growth factors, including the fibroblast and insulin-like growth factors (FGF's and IGF's). In the present study we have investigated whether breast fibroblasts aged in vitro through passage in culture display altered levels of the plasminogen activator system and growth factors that are known to modulate that system. With real-time RT-PCR we found that during passage human breast fibroblasts, whether derived from the tumour burden or from matched adjacent normal breast tissue, exhibited a consistent increase in PAI-1 and FGF-1 and a decrease in MMP-2 mRNA expression. In addition, in 5 out of 7 fibroblast strains we observed an induction of uPA expression in combination with a reduced IGF-1 expression. Interestingly, while during aging MMP-2 protein increased in all tumour-derived fibroblast strains, these protein levels were reduced in all normal tissue- derived fibroblasts. No other clear-cut age-dependent alterations were found in the all-together 25 factors investigated. We furthermore demonstrate in one tumour-derived fibroblast strain that the increases in uPA and PAI-1 mRNA and MMP-2 protein production are inversely related to the telomere length. Artificially increasing telomere length in this fibroblast strain by expressing human telomerase reverse transcriptase (hTERT) prevented senescence and resulted in late passage cultures with early passage uPA, PAI-1 and MMP-2 levels. Our results show that aging accompanied by telomere loss induces PAI-1 and FGF-1 mRNA expression in all breast fibroblast strains, increases uPA and decreases IGF-1 mRNA expression in a subset, and increases MMP-2 protein expression only in tumour-derived breast fibroblasts. These age-induced levels of PAI-1, FGF-1, uPA and MMP-2 in stromal breast fibroblast could contribute to breast cancer progression.

Breast Neoplasms↗
PubMed1992

[Breast feeding after breast reduction].

Few authors have addressed the feasibility of breast-feeding after a reduction mammaplasty. Nowadays, the majority of plastic surgeons perform breast reductions with techniques preserving the continuity of the nipple-areola complex with the retained breast tissue. These pedicle techniques should permit lactation as opposed to the free nipple grafting technique used earlier. To find out how many women nurse their children after a reduction mammaplasty, we reviewed 806 charts to identify 243 women having had a pedicle technique breast reduction, between 1967-1987, at the age of 15 to 35 years. These women were contacted and 98 of them were reached. Eighteen women had become pregnant after their surgery. They agreed to answer a questionnaire regarding their decision to nurse their children, the duration of breast-feeding and the difficulties encountered. Eight of eighteen mothers (45%) nursed their children up to 32 weeks (mean 11 weeks). Among them, 3 nursed for less than 3 weeks and 5 nursed from 3 to 32 weeks (mean 20 weeks). Only one mother had to supplement nursing with formula. Two mothers used mixed formula and breast-feeding when they returned to work. Ten of eighteen mothers (55%) did not breast-feed for the following reasons: 6 by personal choice, 2 due to premature delivery, one was advised that nursing was not feasible and one had no lactation. We believe that the nursing capacity of the breast is preserved after a breast reduction and that women should be encouraged to nurse their children.

Adolescent↗
PubMed2004

[Silicone gel-filled breast implants and breast cancer--an update and safety].

Silicone gel-filled breast implants have long been an important method of breast reconstruction and breast augmentation. In 1992, the Food and Drug Administration (FDA), implemented a voluntary but strongly urged moratorium on the sale and use of silicone gel-filled breast implants. This was due to previous anecdotal reports regarding possible health hazards associated with these types of implants, including the emergence of breast cancer. The FDA allowed the use of silicone gel-filled breast implants for post-mastectomy reconstruction, and also in a small number of breast augmentation patients who were willing to enroll in a long-term prospective study. In this article, we review the current available literature that failed to produce any evidence associating the use of silicone breast implants with the increased risk of breast cancer.

Breast Implants↗
PubMed2005

[Feasibility of breast conservation surgery after neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: To investigate the efficacy of neoadjuvant chemotherapy (NCT) and the feasibility of conservative breast surgery after reducing the size of a primary tumor by NCT in patients with operable breast cancer. METHODS: Thirty patients with stage IIB and IIIA breast cancer underwent NCT including epirubicin 60 mg/m(2) by intravenous injection on day 1 and paclitaxel 150 mg/m(2) by 3-hour continuous infusion on day 2 with 21 days as a cycle from July 2001 to April 2003. All patients received 3 - 4 cycles of NCT. Breast conservation treatment or modified mastectomy was performed after the tumor was reduced to less than 3 cm in diameter. The nonresponders received modified mastectomy. RESULTS: The overall response rate (ORR) was 93% (28/30) for the primary tumors of breast, Fifteen patients (50%) obtained clinical complete response (cCR), including 7 cases (23%) with pathologic complete response (pCR). Thirteen cases (43%) achieved clinical partial response (cPR), and 2 (7%) no change (NC). No case showed progression of disease. Twenty-six (87%) cases were downstaged according to the TNM system classification. The median initial tumor size was 4 cm (3 - 10 cm) before NCT and was reduced to 0.8 cm (0 - 6 cm) after NCT. All 30 patients received operation. Eighteen (60%) of them were candidates for breast conserving therapy, and actually only 11 (37%) selected such surgery. CONCLUSION: An effective treatment for operable breast cancer, NCT with epirubicin plus paclitaxel results in significant downstaging or eliminating of primary tumors in breast cancer, thus expanding the indication of breast conservation therapy.

Adult↗
PubMed2006

[Factors influencing clinical target volume delineation of intact breast in intensity-modulated radiotherapy for breast cancer].

BACKGROUND & OBJECTIVE: In patients with breast cancer who underwent breast conservation treatment, intensity-modulated radiotherapy (IMRT) has been approved to hold better dosimetric advantages and improbable future. Target delineation is the most important process, which determines the accuracy of planning and application of IMRT. However, there is no consensus criterion for the delineation of clinical target volume (CTV) of intact breast. This study was to investigate the factors influencing the delineation of CTV of intact breast in IMRT for breast cancer. METHODS: The CTV of intact breast in 6 patients was delineated by 4 radiation oncologists and 1 radiologist individually, and reference CTV was determined by group consensus. The extent of variation in CTV delineation was quantified by the ratio of common volumes (Vco) of all CTVs to the maximum volume encompassing all CTVs (Vmax). The deviation in the extent of CTV from the extent of reference CTV was quantified in each orthogonal direction to find the origins of variations. In addition, all central lung distances (CLD) in tangential fields, which were designed based on CTVs, were measured. RESULTS: The ratios of Vco to Vmax were low (0.660 and 0.651, respectively) in 2 patients with low glandular density. Among the other 4 patients with high glandular density, the ratio was relatively higher in 2 patients with radio-opaque marks than in the other 2 patients with no marks (0.799, 0.769 vs. 0.735, 0.752, respectively). Compared with reference CTVs, the patients' average deviations of the extent of CTVs were 0 in anterior direction, (1.2+/-3.4) mm in posterior direction, (1.5+/-2.1) mm in cranial direction, (0.7+/-4.1) mm in caudal direction, (0.6+/-3.3) mm in medial direction, and (0.8+/-0.8) mm in lateral direction. The most obvious variations were observed in the area of breast axillary part and primary tumor bed after surgery. The mean CLD in 4 patients exceeded over the conventional limitation of 2 cm. CONCLUSION: The variability between CTVs of intact breast delineated by different radiation oncologists is strongly related to individual glandular density, the extent of breast axillary part, the primary tumor bed after surgery, and the different understanding for lung sparing limitations.

Adult↗
PubMed2006

Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells.

MT1-MMP (membrane type-1 matrix metalloproteinase), otherwise known as MMP14 is a proteolytic enzyme known to be involved in degradating extracellular matrix and assist progression of cancer invasion and progression. We investigated the impact of targeting the expression of MT1-MMP in breast cancer and its clinical relevance. Human breast cancer cell line MDA-MB-231 was used. Expression of MT1-MMP in the breast cancer cell line was manipulated by way of retroviral ribozyme transgene. The in vitro invasion, growth and cell migration were determined on cell lines transfected with either the transgene or control plasmid. Protein and message levels of MMP14 was also assessed using immunohistochemistry and real-time quantitative analysis, and correlated with clinical and pathological information of the patients. Retroviral ribozyme transgene to human MT1-MMP successfully knocked down the levels of MT1-MMP mRNA from MDA-MB-231 cells. Reduction of MT1-MMP from the breast cancer cells resulted in significant reduction of in vitro invasiveness and loss of response to an invasion stimulus, HGF, compared with control and wild-type cells. The invasion index for MT1-MMP knockdown cells were 13+/-3.1 (without HGF) and 16.4+/-2.3 (with HGF, p=0.14), and the index for transfection control cells 25.3+/-4.3 (without HGF) and 40.4+/-4.1 (with HGF, p=0.0049). Transfection with the transgenes did not change the rate of cell growth. In clinical breast cancer, MT1-MMP staining was both membranous and cytoplasmic. Tumour cells displayed stronger staining compared with normal mammary epithelial cells. Tumour tissues had a marginally higher levels of the MMP14 transcript (8.6+/-1.9), compared with normal tissues (4.7+/-1.4), p=0.13. No significant difference was observed between node positive and node negative tumours (9.0+/-2.2 vs 8.7+/-3.1, p=0.24). Marginally higher levels of the MMP14 transcript were seen in tumours which developed metastasis and local recurrence. However, tumours from patients who died of breast cancer related causes had significantly higher levels of the transcript, compared with tumours from patients who remained disease-free 10 years after initial surgery (12.2+/-2.5 vs 6.3+/-1.2, p=0.0091). MT1-MMP is a proteolytic enzyme that is pivotal in controlling the invasiveness of breast cancer cells. It is highly expressed in aggressive breast tumours and is associated with clinical outcome. The enzyme is a potential therapeutic target in breast cancer.

Breast Neoplasms↗
PubMed1983

Antibody reacting with the murine mammary tumor virus in the serum of patients with breast carcinoma: a possible serological detection method for breast carcinoma.

Sera from patients with Stages A and B infiltrating ductal carcinoma of the breast, benign breast disease, cancers other than breast carcinoma, and normal female controls were examined by indirect immunoelectron microscopy (IEM) and a viral agglutination test for evidence of antibodies directed against murine mammary tumor virus (MMTV). Sera from 41 (79%) of 52 patients with breast carcinoma and eight (19%) of 42 normal subjects or patients with benign breast disease (noncancer subjects) showed evidence of MMTV labeling by IEM. In the MMTV agglutination test, significant virus agglutination (2+ to 4+) was present in eight (13%) of 61 noncancer sera, 58 (86%) of 68 breast carcinoma sera, and two (11%) of 18 other cancer sera. The results of the more rapid MMTV agglutination test correlated well with IEM. Analysis of reacting antibody by IEM revealed no immunoglobulin A and significant immunoglobulin M and immunoglobulin G antibody. Serum reactivity against MMTV was completely absorbed by MMTV but not by the glycoprotein with a molecular weight of 52,000 of MMTV, Friend murine leukemia virus, avian myeloblastosis virus, or sheep erythrocytes. It is concluded that reactivity of human antibodies to MMTV is strongly associated with, but is not entirely specific for, breast carcinoma. It remains to be determined if normal persons with these antibodies will ultimately develop breast cancer and should therefore be considered at high risk. These tests may have potential usefulness as a diagnostic screen for breast cancer.

Agglutination↗