Prognosis in women with breast cancer and private extra insurance coverage.

BACKGROUND: Many women covered by the Spanish public health system also have an extra private insurance policy for gynecological examinations and routine annual mammography. We retrospectively analyzed the long-term survival rates in these patients when diagnosed with breast cancer. METHODS: We analyzed the survival and prognostic factors in patients diagnosed with breast cancer who were referred to a medical oncology unit for multidisciplinary treatment covered by private health insurance. RESULTS: Between 1994 and 2009, a total of 434 patients with breast tumor were analyzed: 33 in situ and 401 infiltrating. Among the infiltrating carcinomas, 38 were stage IV and 363 were stage I, II, or III. With a median follow-up of 62 months, the 5-year global survival rate was 91%: 97% for stage I, 94% for stage II, and 77% for stage III tumors. In the patients diagnosed by routine mammography, the 5-year survival rate was 96%, compared with 86% in those consulting their gynecologist after breast self-examination or for other symptoms (p=0.0159). Seventy-four percent were treated conservatively and experienced better survival than the 26% who underwent mastectomy (p=0.0024). Patients with disease with positive hormone receptors had a better survival rate (p=0.0264); hormone receptor status was the only independent prognostic factor in the Cox multivariate analysis. Postmenopausal patients who received adjuvant tamoxifen plus exemestane had a better prognosis than those who received tamoxifen alone (p=0.0203). CONCLUSIONS: Long-term survival rate was high in breast cancer patients with extra private insurance coverage. This is probably because disease was diagnosed at an early stage.

Prospective evaluation of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) in patients with primary locoregional breast cancer.

BACKGROUND: The utility of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) as prognostic factors in primary breast cancer is unclear. METHODS: We prospectively studied CEA and CA 15.3 in the sera of 2062 patients with untreated primary breast cancer diagnosed between 1984 and 2008. RESULTS: Increased CEA (>5 microg/L) and CA 15.3 (>30 kU/L) concentrations were found in 12.7% and 19.6% of the patients, respectively, and 1 or both tumor markers were increased in 28% (570 of 2062). Increases in each tumor marker correlated with larger tumor sizes and nodal involvement. Tumor size, estrogen receptor (ER), and CEA were independent prognostic factors by multivariate analysis in the total group [disease free survival (DFS) and overall survival (OS)] as well as in node-positive (NP) and node-negative (NN) patients. Nodal involvement and histological grade were independent prognostic factors in the total group as well as in NP patients. By contrast, adjuvant treatment and CA 15.3 were independent prognostic factors only in NN patients (DFS and OS). All patients with CEA >7.5 microg/L had recurrence during follow-up. Use of both tumor markers allowed discrimination of the groups of risk in T1 NN patients: 56.3% of recurrences were seen when 1 or both tumor markers were increased, whereas only 9.4% of recurrences were seen in T1 NN patients without increases of either marker. CONCLUSIONS: CEA and CA 15.3 are useful prognostic factors in NP and NN breast cancer patients. CEA >7.5 microg/L is associated with a high probability of subclinical metastases.

Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value.

Tumor markers were studied in the sera of 883 untreated patients with primary breast cancer diagnosed between 1989 and 2007. Abnormal human epidermal growth factor receptor 2 (HER-2)/neu levels (>15 ng/mL) were found in 9.5%, carcinoembryonic antigen (CEA) in 15.9%, and cancer antigen (CA) 15.3 in 19.7% of the patients. One or more tumor markers were abnormal in 305 (34.5%) of the 883 studied patients. Significantly higher serum HER-2/neu levels were found in patients with tissue overexpression of this oncoprotein (p < 0.0001). CEA, CA 15.3, and HER-2/neu (only in those patients with tissue overexpression) serum levels were related with tumor stage (tumor size and nodal involvement) and steroid receptors (higher values in estrogen receptor-negative (ER-) tumors). Univariate analysis showed that HER-2/neu serum levels were prognostic factors in disease-free survival (DFS) and overall survival (OS) only in patients with tissue overexpression. Multivariate analysis in 834 patients show that nodal involvement, tumor size, ER, CEA, and adjuvant treatment were independent prognostic factors in DFS and OS. When only patients with HER-2/neu overexpression in tissue were studied, tumor size, nodal involvement, and tumor markers (one or another positive) were independent prognostic factors for both DFS and OS. HER-2/neu serum levels were also an independent prognostic factor, with CEA, ER, and nodes in 106 patients treated with neoadjuvant treatment. In summary, serum HER-2/neu, CEA, and CA 15.3 are useful tools in the prognostic evaluation of patients with primary breast cancer.

Predicting non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement: evaluation of two scoring systems.

The aim of this study was to validate a nomogram and a scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node (SLN) involvement. A total of 516 breast cancer patients underwent sentinel lymph node biopsy at our institution from January 2001 to August 2006. A prospective database was used to identify breast cancer patients with a positive SLN biopsy examination who underwent a completion axillary lymph node dissection. A total of 114 patients were identified. The Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and an axilla scoring system from Paris (Hôpital Tenon) were used to predict the probability of having non-SLN involvement. One hundred fourteen patients were included in the study. The areas under the receiver operating characteristics (ROC) curves were 0.671 (95% CI: 0.552-0.790) for the MSKCC nomogram and 0.703 (95% CI: 0.596-0.811) for the Tenon score. The univariate analysis shows that size of SLN metastases, the number of positive and negative SLN and the proportion of positive SLN were statistically significant. On multivariate logistic regression analysis, the size of SLN metastases and the proportion of positive SLN were statistically significant. The two scoring systems are similar according to their area under ROC curves, but should be improved to be valid and determinant to the general population. Meanwhile, the use of scoring systems could be applied in an individual manner in some patients.

Preoperative MRI of pure intraductal breast carcinoma--a valuable adjunct to mammography in assessing cancer extent.

The aim of the study was to evaluate the contribution of preoperative breast magnetic resonance imaging (MRM) as an adjunct to mammography in assessing extent of pure ductal carcinoma in situ (DCIS) and to relate magnetic resonance imaging (MRI) findings to histopathological features. A retrospective analysis was conducted of 86 histologically proven cases of pure DCIS of the breast. Two experienced radiologists with knowledge of clinical and histopathological findings at the time of the review evaluated mammographic and preoperative MRI results by consensus. Compared to histopathology, mammography or MRM alone underestimated DCIS extent in 18.6% and 31.4% of cases, respectively. When both imaging modalities were considered, DCIS extent was underestimated in 8% of cases. Combined use of mammography and MRM revealed good agreement with histopathology to assess DCIS extent (kappa=0.439; P<0.001). MR enhancement of DCIS was related to histologic size (P=0.011). Mammography is more accurate than MRM in assessing cancer extent of pure DCIS, but combined use of both imaging techniques leads to improved accuracy.

Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan.

PURPOSE: To analyze the frequency in determining pathologically proven metastatic involvement of internal mammary nodes (IMN) after sentinel lymph node (SLN) technique in breast cancer and to evaluate the implications for radiotherapy (RT) management of patients. METHODS AND MATERIALS: Two hundred and twenty-five patients who underwent lymphatic mapping for early breast cancer treated with breast-conserving surgery and radiation (80%) or mastectomy (20%) were evaluated. There were two phases in the study: the validation phase (105 patients, 52 T1, 53 T2 < or = 4 cm), and the application phase (120 patients, 70 T1, 50 T2 < or = 2.5 cm). In the validation, if a drainage pathway to the IMN was identified, no biopsy was performed in this phase. In the application, if the study showed metastases in the IMNs, biopsy was performed. When histologically proven IMN metastases were detected, RT was included on the IMN chain planned with a 3D treatment system using conformal techniques. At the beginning of the study the injection site was subdermal and subsequently, the injection site was changed to peritumoral and intratumoral to search for IMN. RESULTS: In 31 patients of 225 (14%) hot spots were observed in the internal mammary chain (11.5% and 17.2% in the validation and application phases, respectively). In the validation phase, in 11 cases (11.5%) IMN drainage was observed, and in the application phase, in 20 cases (17.2%). Sampling of the internal mammary basin based on lymphoscintigraphy results was successful in 69% of the cases (14 of 20) and revealed metastatic involvement in 14% (2 of 14). This represents incidence of only 1.7% (2 of 116) in early breast cancer patients with SLN study in the application phase. In both cases the axillary SLN was also positive. Both patients with metastatic involvement of the IMN area received RT on the IMN chain next to the remaining breast after conservative surgery. CONCLUSIONS: We can conclude that 14% of the patients with intraoperative drainage into the IMN surgical examination of the lymph nodes had pathologically positive metastases. The percentage in pathologically proven metastatic involvement of IMN after the SLN technique in early breast cancer is low, but it is not negligible. Moreover, it is expected to increase since the international recommendations have established a 3-cm cutoff for practicing the SLN technique. Although the real value of IMN irradiation in early breast cancer is not known, including this chain in postoperative radiotherapy is not recommended unless pathologically proven IMNs have been produced by the SLN technique. To avoid overdosage or underdosage in the joint between the medial tangential and IMN fields, an individualized 3D dosimetry study is mandatory to enhance dose distribution and reduce the heart volume to lessen side effects.

Added value of intraoperative real-time imaging in searches for difficult-to-locate sentinel nodes.

UNLABELLED: Localization of sentinel lymph nodes can be challenging if they are in difficult anatomic locations or near high radiotracer activity. The purpose of this study was to assess the value of intraoperative real-time imaging using a portable gamma-camera in conjunction with a conventional gamma-counting probe when it is difficult to localize the sentinel node. METHODS: After (99m)Tc-nanocolloid injection, patients with various malignancies underwent presurgical lymphoscintigraphy followed by surgery (usually the next day). We evaluated 20 patients who required sentinel lymph node biopsy and in whom the location or other characteristics of the sentinel node would make intraoperative retrieval difficult. During surgery, the sentinel node was localized using a portable gamma-camera together with a hand-held gamma-probe. A (153)Gd pointer or (125)I seed was used to better depict the sentinel node location in real time. RESULTS: Using only a conventional hand-held gamma-probe, surgeons were able to definitively localize the sentinel node in 15 of 20 patients. Intraoperatively, the portable gamma-camera showed uptake by the definite sentinel node in 19 of 20 patients and helped to precisely localize the node with the hand-held gamma-probe in 4 patients. In 1 of these patients, the sentinel node was metastatic. CONCLUSION: The combination of a standard hand-held gamma-probe and real-time imaging provided by a portable gamma-camera offers a high intraoperative detection rate in patients with difficult sentinel node localization as assessed by presurgical lymphoscintigraphy.

Exeresis and brachytherapy as salvage treatment for local recurrence after conservative treatment for breast cancer: results of a ten-year pilot study.

PURPOSE: To analyze the long-term results of a pilot study assessing excision and brachytherapy as salvage treatment for local recurrence after conservative treatment of breast cancer. METHODS AND MATERIALS: Between December 1990 and March 2001, 36 patients with breast-only recurrence less than 3 cm in diameter after conservative treatment for Stage I or II breast carcinoma were treated with local excision followed by high-dose rate brachytherapy implants (30 Gy in 12 fractions over a period of 5 days). No patient was lost to follow-up. Special attention was paid to local, regional, or distant recurrences; survival; cosmesis; and early and late side effects. RESULTS: All patients completed treatment. During follow-up (range, 1-13 years), 8 patients presented metastases (2 regional and 6 distant) as their first site of failure, 1 had a differed local recurrence, and 1 died of the disease. Actuarial results at 10 years were as follows: local control, 89.4%; disease-free survival, 64.4%; and survival, 96.7%. Cosmetic results were satisfactory in 90.4%. No patient had Grade 3 or 4 early or late complications. Of the 11 patients followed up for at least 10 years, all but 1 still had their breast in place at the 10-year stage. CONCLUSIONS: High-dose rate brachytherapy is a safe, effective treatment for small-size, low-risk local recurrence after local excision in conservatively treated patients. The dose of 30 Gy of high-dose rate brachytherapy (12 fractions over a period of 5 days twice daily) was well tolerated. The excellent results support the use of breast preservation as salvage treatment in selected patients with local recurrence after conservative treatment for breast cancer.

MRI of metaplastic carcinoma of the breast.

OBJECTIVE: The purpose of our study was to describe the MRI findings of metaplastic carcinoma of the breast and to compare those findings with underlying histopathologic features. CONCLUSION: Metaplastic carcinoma of the breast shows high signal intensity on T2-weighted MRI. This finding is related to the necrotic component of the tumor and may be useful for preoperative diagnosis of metaplastic carcinoma of the breast, although it must be differentiated from mucinous carcinoma and, less frequently, necrotic infiltrating ductal carcinoma.

A practical approach to intraoperative evaluation of sentinel lymph node biopsy in breast carcinoma and review of the current methods.

BACKGROUND: Sentinel lymph node (SLN) biopsy is increasingly becoming an alternative method for assessing axillary status in breast carcinoma patients. Intraoperative SLN evaluation can potentially select patients for immediate axillary clearance and spare most of them a second surgical procedure. Nevertheless, no standard protocol for intraoperative SLN evaluation has been developed. The aims of this study were to establish the reliability of SLN intraoperative evaluation in breast carcinoma staging, to review the published methods currently used, and to propose a standard protocol. METHODS: One hundred fifty-two SLNs were collected from 86 patients. Lymphoscintigraphy, blue dye, and gamma camera intraoperative controls were used for localization. Each SLN was sliced 2 mm thick and was intraoperatively evaluated by using the combination of frozen section and imprint cytology. The final examination included standard hematoxylin and eosin staining, and, in case of persistent negativity, further sectioning, including hematoxylin and eosin combined with immunohistochemistry (CAM5.2 cytokeratin), was performed. RESULTS: The combination of frozen section and imprint cytology for intraoperative SLN evaluation yielded an intraoperative sensitivity of 78% and a specificity of 100%. All macrometastases (>2 mm) were detected during surgery, as were 2 micrometastases. Final examination detected seven more micrometastases, six of which consisted of isolated tumor cells. CONCLUSIONS: We propose a fast, cost-effective, and accurate procedure for SLN evaluation that is useful for making intraoperative decisions, feasible for most institutions, and reliable because of its high sensitivity (100% for macrometastases) and specificity.

Clinical relevance of sentinel lymph nodes in the internal mammary chain in breast cancer patients.

PURPOSE: Despite the widespread use of sentinel lymph node (SLN) biopsy in breast cancer patients, some controversy exists about the correct management of extra-axillary nodes, especially those located in the internal mammary chain. The aim of this study was to evaluate the incidence of SLNs in this region, calculate the lymphoscintigraphic and surgical detection rates and evaluate the clinical impact on staging and therapeutic decisions. METHODS: The study involved 383 consecutive women diagnosed with early breast cancer with T1 or T2 tumours. Eight patients had a bilateral tumour, which brought the total to 391 lesions. Lymphoscintigraphy was performed on the day before surgery by injection of (99m)Tc-labelled nanocolloid. The injection site was subdermal (68 patients), peritumoural (107 patients) or intratumoural (216 patients). During surgery a gamma probe was used to guide the surgeon and the SLNs were removed. SLNs were analysed by a conventional pathological study and processed for H&E examination and immunohistochemistry. RESULTS: Lymphoscintigraphy detected at least one SLN in 369 out of the 391 procedures (94.4%). SLNs were found in the axillary chain in 367 cases and in the internal mammary chain in 55. In two of these 55 cases (3.6%), the SLN was the only one detected. There was no drainage to the internal mammary chain in any case of subdermal injection but such drainage was found in 15.9% of cases with peritumoural injection and 17.6% of those with intratumoural injection. Compared with tumours located in the outer quadrants, a higher percentage of tumours located in the inner quadrants showed drainage to the internal mammary chain (p<0.001). A total of 42 SLNs in the internal mammary chain could be removed in 32 patients without appreciable morbidity. In 20 cases both axillary and internal mammary SLNs were negative, in four both were positive, and in five axillary SLNs were positive and internal mammary SLNs were negative. More interestingly, in the remaining patient with both axillary and internal mammary SLNs, the axillary SLN was negative while malignant cells were found in the internal mammary region. In the evaluation of the clinical impact of internal mammary SLN biopsy, we found that staging was modified from pN1a to pN1c in four patients and, more importantly, from pN0 to pN0(i+) in one patient. The change in stage led to a modification of the postoperative treatment plan with respect to radiotherapy and systemic therapy. CONCLUSION: Evaluation of the SLNs in the internal mammary chain provides more accurate staging of breast cancer patients. If internal mammary sampling is not performed, patients can be understaged. This technique can offer a better indication of those patients who will benefit from selective treatment options like radiotherapy to this region or systemic therapy.