Serum HER-2 extracellular domain: relationship with clinicobiological presentation and prognostic value before and after primary treatment in 701 breast cancer patients.

PURPOSE: To determine the clinical correlations and prognostic value of serum HER-2 (sHER-2) before and after primary breast cancer treatment. METHODS: sHER-2 from 701 consecutive patients with stage I-III tumors (median follow-up 7.7 years) was assayed by an enzyme-linked immunosorbent assay (Immuno 1, Bayer Diagnostics). RESULTS: The median pretreatment sHER-2 concentration was 8.30 ng/mL (range 3.15-82.00 ng/mL). Forty-seven patients (6.7%) had sHER-2 concentrations >12 ng/mL (cutoff level). Pretreatment sHER-2 correlated positively with CA 15.3 (p=0.0169), pathological tumor size (p=0.0082), number of invaded lymph nodes (pN, p=0.0160) and histological grading (p=0.0086). Kaplan-Meier analyses indicated that pretreatment sHER-2 was of prognostic value for contralateral breast cancer (p=0.0018), metastasis-free survival (MFS) (p=0.0008) - particularly lung (p=0.0082) and liver metastases (p=0.0035) - and overall disease-specific survival (DSS) (p=0.0020). According to pN status, pretreatment sHER-2 was of prognostic value only for pN-positive patients (p=0.0017). When combined with estradiol or progesterone receptor status, patients with elevated sHER-2 and receptor-negative tumors had a significantly shorter DSS (p<0.0001 for both receptors). Post-treatment sHER-2 also had individual prognostic value for MFS (p=0.0144) and DSS (p=0.0212). In multivariate analysis, only sHER-2 after primary treatment was an independent prognostic variable for MFS and DSS (p=0.0078 and p=0.0058, respectively). CONCLUSION: sHER-2 elevation in early breast cancer correlates with the principal criteria of tumor aggressiveness, thus permitting selection of patients with a high risk of visceral metastases and contralateral breast tumors. Post-treatment sHER-2 is an independent prognostic factor enabling to identify patients likely to benefit from aggressive adjuvant treatments.

Prognostic value of CA 15.3 kinetics for metastatic breast cancer.

Up to 80% of breast cancer patients developing metastases have high levels of CA 15.3. We studied the prognostic implications of CA 15.3 kinetics in 119 patients before and at first metastasis by univariate and multivariate statistics. At first metastasis, CA 15.3 was elevated in 82.4% of patients, with a lead time (median 162 days) in 42.0% of them. Kaplan-Meier analysis showed overall survival (median 1477 days) to be significantly related to estrogen receptor (ER) and progesterone receptor (PgR) status (p=0.0001) and tumor size (p=0.025). The interval between diagnosis and first abnormal CA 15.3 (p=0.0001), the CA 15.3 concentration (p=0.013), and the presence or absence of a lead time (p=0.001) also had prognostic value. ER and PgR status (p=0.0005 and p=0.0103, respectively), metastasis-free interval (p=0.0003), existence of a CA 15.3 lead time (p=0.0028), and days from diagnosis to first abnormal CA 15.3 (p=0.0055) entered in the Cox model. After first metastasis (median survival 573 days), ER and PgR status (p=0.0001 and p=0.0004, respectively), existence of a lead time for CA 15.3 (p=0.0138), and the concentration of first abnormal CA 15.3 (p=0.0145) had individual prognostic value. In the Cox model ER status (p=0.0001), nodal status (p=0.0191), existence of a lead time for CA 15.3 (p=0.0033), days from diagnosis to first abnormal CA 15.3 (p=0.0132), and concentration of first abnormal CA 15.3 (p=0.0320) were found to be independent prognostic variables. Compared to a matched historical control group that was not monitored by CA 15.3 assaying (n=140), the study group had a significantly longer survival after the first metastasis (p=0.0005). In conclusion, the kinetics of CA 15.3 before the first metastasis is of prognostic value. When associated with 18-fluorodeoxyglucose imaging, serial CA 15.3 assays may help to implement early treatment of metastases.

Improved survival after one course of perioperative chemotherapy in early breast cancer patients. long-term results from the European Organization for Research and Treatment of Cancer (EORTC) Trial 10854.

The aim of this study was to examine whether one course of perioperative polychemotherapy yields better results in terms of survival, progression-free survival (PFS) and locoregional control than surgery alone in early stage breast cancer. From 1986 to 1991, 2795 patients with stage I/II breast cancer were randomised to receive either one perioperative course of an anthracycline-containing chemotherapeutic regimen within 36 h after surgery or surgery alone. Patients were followed-up for overall survival, PFS and locoregional recurrence. The median follow-up period at time of the analysis was 11 years. PFS and locoregional control were significantly better (P=0.025 and P=0.004, respectively) in the perioperative chemotherapy arm. Node-negative patients seemed to benefit most from the perioperative FAC. Patients who received perioperative chemotherapy and locoregional therapy alone had significantly better overall survival rates than patients who received locoregional therapy alone (P=0.004). Patients who received additional systemic therapy did not seem to benefit from one course of perioperative chemotherapy (P=0.65). One course of perioperative polychemotherapy does improve PFS and locoregional control in early stage breast cancers. This effect is still present after 11 years of follow-up.

Detection of occult disease in breast cancer using fluorodeoxyglucose camera-based positron emission tomography.

An isolated increase of blood tumor marker CA 15.3 in breast cancer is considered a sensitive indicator for occult metastatic disease but by itself is not sufficient for initiating therapeutic intervention. We investigated the potential of camera-based positron emission tomography (PET) imaging using [18F]-fluorodeoxyglucose (FDG) to detect clinically occult recurrences in 132 female patients (age, 35-69 years) treated for breast cancer, all presenting with an isolated increase in blood tumor marker CA 15.3 without any other evidence of metastatic disease. FDG results were correlated to pathology results or to a sequentially guided conventional imaging method. One hundred nineteen patients were eligible for correlations. Positive FDG scans were obtained for 106 patients, including 89 with a single lesion and 17 with 2 or more lesion. There were 92 true-positive and 14 false-positive cases, 10 of which became true positive within 1 year. Among the 13 negative cases, 7 were false negative and 6 were true negative. Camera-based PET using FDG has successfully identified clinically occult disease with an overall sensitivity of 93.6% and a positive predictive value of 96.2%. The smallest detected size was 6 mm for a lymph node metastasis (tumor to nontumor ratio, 4:2). FDG camera-based PET localized tumors in 85.7% of cases suspected for clinically occult metastatic disease on the basis of a significant increase in blood tumor marker. A positive FDG scan associated with an elevated CA 15.3 level is most consistent with metastatic relapse of breast cancer.

Is adjuvant tamoxifen recommended in post-menopausal node-negative breast cancer patients with high estrogen receptor values?

The impact of ER levels on the response to tamoxifen was evaluated in 1,623 postmenopausal primary breast cancer patients treated at our center (median follow-up 8.2 years). In patients receiving adjuvant tamoxifen a significantly longer disease-free survival (DFS) was observed when ER levels were elevated (p<0.00001). Very high ER (>424 fmol/mg protein) appeared to be detrimental in node-negative patients not treated with tamoxifen.

Serum bFGF (basic fibroblast growth factor) and CA 15.3 in the monitoring of breast cancer patients.

BACKGROUND: Basic fibroblast growth factor (bFGF) is a potent angiogenetic factor which may influence breast cancer evolution. MATERIALS AND METHODS: Serum bFGF, (cut-off 10 pg/ml), was assayed in 166 breast cancer patients at all stages and compared with CA 15.3. RESULTS: In 99 pre-treatment (PT) sera, 39/99 (39.4%) were bFGF positive, 9/99 (9.1%) CA 15.3 positive (> 30 U/ml), and not correlated. No correlations were found between bFGF and age, menopausal status, TNM or pTNM, histology, SBR grading or steroid receptors. A postoperative decline in bFGF positivity, from 30.8 to 7.7% (n = 39), was observed. An abnormal CA 15.3 after primary treatment (n = 2/39) was of bad prognosis (P < 0.0001), whereas positive bFGF (n = 3/39) had no univariate prognostic value (median follow-up 5.5 years). During follow-up, positive bFGF was recorded in 6/92 (6.5%) disease-free patients (DFS), 13/15 (86.7%) regressions, 8/16 (50.0%) stable disease, and 46/67 (68.7%) progressive disease (significant differences between PT or DFS and post recurrence levels (P < 0.001), and between relapse before and after treatment (P = 0.002)). CONCLUSION: Serum bFGF is more often elevated before treatment or after relapse than in DFS, and rises under systemic treatments. Its pattern of variations does not add to CA 15.3 for breast cancer monitoring.

Contrast-enhanced CT: value for diagnosing local breast cancer recurrence after conservative treatment.

PURPOSE: To assess contrast material-enhanced computed tomography (CT) of breast for diagnosing local recurrence after conservative therapy. MATERIALS AND METHODS: In 111 patients, 118 lesions were evaluated with unenhanced and enhanced CT. Criterion for cancer recurrence was detection of a lesion with an enhancement of 45 HU or more. RESULTS: One group comprised 52 lesions with pathologic diagnoses, obtained within 1 month of CT, of malignancy in 43 and benignancy in nine. Scans were positive in 40 of 43 recurrences and negative in six of nine benign lesions. Seventeen recurrent lesions were nonpalpable, and contrast-enhanced CT results were true-positive in 15 of these. A second group comprised 66 lesions with a mean follow-up of the treated breast of 28 months after CT. In 56 lesions, the scans were negative, with no recurrence in 55; local recurrence was proved with a 14-month delayed surgical biopsy in one. In 10 lesions, scans were positive, with a delayed diagnosis of recurrence 5 and 6 months after CT in two and no evidence of recurrence in eight (false-positive results). The sensitivity of breast CT for both groups was 91% (42 of 46 lesions) with a specificity of 85% (61 of 72 lesions). CONCLUSION: Contrast-enhanced CT is sensitive in the diagnosis of local recurrence of breast cancer, even in nonpalpable lesions, and may be a useful tool in patients with equivocal clinical and/or mammographic findings during follow-up after conservative therapy.

Improved local control and disease-free survival after perioperative chemotherapy for early-stage breast cancer. A European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study.

PURPOSE: To investigate whether a short intensive course of perioperative polychemotherapy can change the course of early breast cancer. PATIENTS AND METHODS: A total of 2,795 women with early breast cancer, stage I to IIIA, were randomized onto a trial (European Organization for Research and Treatment of Cancer [EORTC] 10854) to compare surgery followed by one course of perioperative chemotherapy versus surgery alone. Patients assigned to the chemotherapy arm received one course of fluorouracil 600 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 600 mg/m2 (FAC) intravenously, within 24 hours after surgery. In both randomized treatment arms, a recommendation was made for premenopausal women with positive axillary nodes to receive prolonged courses of cyclophosphamide, methotrexate, and fluorouracil (CMF), according to the standard treatment for this subgroup. RESULTS: At a median follow-up time of 41 months, local control was significantly better in the perioperative treatment arm as compared with the observation arm (hazards ratio, 0.60; 95% confidence interval, 0.44 to 0.83; P < .01). Disease-free survival was significantly prolonged in the chemotherapy arm (hazards ratio, 0.84; 95% confidence interval, 0.70 to 0.99; P = .04). Premenopausal node-negative patients especially showed an advantage for the perioperative chemotherapy arm. No advantage for perioperative chemotherapy was observed in premenopausal node-positive women who also had received prolonged chemotherapy. CONCLUSION: We conclude that one course of perioperative FAC is able to improve local control and can prolong disease-free survival in women with early breast cancer. However, our results also suggest that a perioperative timing cannot improve the results of standard prolonged chemotherapy in premenopausal women with positive axillary nodes.

[Local recurrence after conservative therapy of breast cancer: risk factors, site of recurrence, evolution]. / Récidives mammaires après traitement conservateur du cancer du sein: facteurs de risque, topographie des récidives, évolution.

The identification of factors associated with breast recurrence as first event (62 cases, 10%) following conservative surgery and radiation therapy are drawn out from a series++ of 618 mammary carcinomas of clinical size less than 40 mm, stage I and II (UICC), with a median follow up of 8 years. The most powerful predictive characteristic associated with the likelihood of breast recurrence is multiple foci of invasion (42.9% vs 8.9, P = 0.0001, relative risk [RR]: 6). After this rarely cited feature, young age, less than 40 years (20% vs 7.3%, P = 0.0001, RR: 2.8), extensive in situ carcinoma more than 25% (19.2% vs 8.7%, P = 0.003, RR: 2.5) were found also persistent in the Cox model, but not histologic size more than 25 mm (18.9% vs 9.1%, P = 0.01, RR: 2.3). The site of recurrence was studied on the 54 salvage mastectomy done. A high rate of recurrence at distance of the initial site was found: 37% whose more than half, 22%, were multicentric. No significant difference in the mean delay of appearance was noted between recurrence near or at distance of the initial cancer (mean delay 52 months vs 64 months). From the recurrence the evolution is not very favourable: excluding simultaneous metastases found at the preoperative investigation, ten cases, mammary recurrence is followed by a metastatic syndrome in 36% of cases against 17% without it (P = 0.01, RR: 1.9). Metastatic evolution is not significantly linked with the time, early or late, of the mammary recurrence (54.5% before 5 years vs 39% after) but with the association of a controlateral cancer (P = 0.03). Locally ten of the 54 mastectomy presented a thoracic recurrence, often in case of multicentric breast recurrence (P = 0.05) and not significantly when skin or areola were invaded by carcinoma.

Thromboembolic complications after perioperative chemotherapy in women with early breast cancer: a European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group study.

PURPOSE AND METHODS: Data from a randomized phase III trial in early breast cancer, comparing surgery followed by one short intensive course of perioperative fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus surgery alone, were analyzed for the occurrence of thromboembolic complications within 6 weeks after surgery. RESULTS: Twenty-seven of 1,292 patients assigned to the perioperative chemotherapy treatment arm (2.1%) and 10 of 1,332 patients on observation (0.8%) developed thromboembolic events (P = .004). The frequency of thromboembolic complications was higher among postmenopausal women compared with premenopausal women (2.0% v 0.6%, P = .003). Patients who had mastectomy had a higher frequency of thromboembolic disease than those who had tumorectomy (2.3% v 0.7%, P < .001). Three deaths occurred after pulmonary embolism, all of them in the perioperative chemotherapy treatment arm. CONCLUSION: These results suggest a contributing role of perioperative chemotherapy to thromboembolic disease, especially in postmenopausal women and women undergoing mastectomy. Antithrombosis prophylaxis should be considered in the case of adjuvant perioperative chemotherapy.

Prognostic value of a solubilized fraction of EGF receptors in primary breast cancer using an immunoenzymatic assay--a retrospective study.

In a retrospective study of 319 primary breast cancers, we show that an immunoenzymatic assay of a solubilized fraction of EGF receptors indicates a prognostic value for EGFR which is in contradiction with some (but not all) other studies. It appears that different methodological approaches of measuring EGFR are not equivalent in terms of prognostic power. We emphasize the need for rigorous multicentric standardization and quality control of assays, followed by multistep validation of parameters oriented towards clinical use.

[Role of radiotherapy in the treatment of bone metastases]. / Place de la radiothérapie dans le traitement des métastases osseuses.

The most frequently encountered metastases during evolution of cancers are bone metastases, which involve painful syndrome. External radiotherapy is an effective and indisputable treatment to give relief to suffering patients. The modalities of the regimen of external radiotherapy are different according to the disease stage, the prognosis and eventually associated treatments such as chemotherapy, hormonotherapy or surgery. The dose can be delivered either according to normal regimen, hypofractionated radiotherapy, or half-body radiotherapy. Whatever the modalities, antalgic results noted in around 85% cases are very similar. On the other hand, the plastic action of external radiotherapy on lytic bone is also important.

[An unusual way of manifesting acute granulocytic leukemia: granulocytic sarcoma of the breast. Apropos of a case with trisomy 22]. / Un mode inhabituel de révélation des leucémies aiguës granuleuses: le sarcome granulocytaire du sein. A propos d'un cas porteur d'une trisomie 22.

A case of granulocytic breast sarcoma in a 19 year-old-girl is reported. Surgical excision of the tumor was followed by radiotherapy of the breast and lymph nodes. Then 3 months later acute M2 myelocytic leukemia was diagnosed, complete remission being attained using rubidazone-cytarabine and maintained by monthly reinduction courses. Trisomy of chromosome 22 was present in leukemic cells and disappeared during remission. Its pathogenic significance is briefly discussed.

[Metastatic malignant thymoma]. / Thymomes malins métastatiques.

Three cases of metastatic malignant thymoma are reported. In all three cases the tumour was invasive and excision was only partial or impossible. Histologically, these tumours were of epithelial origin with a variable lymphocytic component. Metastases were initially present in one case and in the other two developed within the first year. Partial remission was obtained with different drug combinations in only one case, and it was of short duration. The authors emphasize the increased frequency and poor prognosis of these tumours and the need for multiple chemotherapy and loco-regional treatment in the management of invasive thymomas.

[Acute lymphoblastic leukemia secondary to Ewing's sarcoma treated by a combination of surgery-radiotherapy-chemotherapy]. / Leucémie aiguë lymphoblastique secondaire à un sarcome d'Ewing traité par association chirurgie-radiothérapie-chimiothérapie.

An acute lymphocytic leukaemia develops in a fourteen years old boy, treated five and a half years earlier for an Ewing's sarcoma of the right fibula, by an association of surgery, radiotherapy and chemotherapy. The Ewing's sarcoma is still in remission. Chemotherapy induces easily a complete remission. The authors discuss the links between the two malignancies and their treatment.

[Chronic lymphoid leukemia with erythroblastopenia and primary liver tumor]. / Leucémie lymphoïde chronique avec érythroblastopénie et tumeur primitive du foie.

Erythroblastopenia occurred in the course of chronic B cell lymphocytic leukemia. The failure of chlorambucil therapy prompted the decision of thymic irradiation. This was effective on the lymphoid proliferation but did not modify the erythroblastopenia. Progressive hepatomegaly led to the diagnosis of hepatoma.

[Irradiation of the thymus region in chronic lymphoid leukaemia. Seven cases (author's transl)]. / Irradiation de la loge thymique dans la leucémie lymphoïde chronique. 7 observations.

7 patients with chronic lymphatic leukemia, B type, have been treated with thymic irradiation. A full remission was achieved in 2 and a partial one in 4. No serious complications were noted during or after the irradiation. This treatment has proved efficient even after the failure of a previous chemotherapy and has permitted to resume any other therapeutic modality when the C.L.L. is no more controlled.

[Results of concentrated curative radiotherapy in skin epitheliomas and bladder tumours (author's transl)]. / Résultats de l'irradiation concentrée à visée curatrice dans les épithéliomas cutanés et les tumeurs vésicales

So-called concentrated irradiation (3,000 rads in 5 sessions spread over 1 month or 4,000 rads over 7 sessions during 2 months) gave disappointing results in skin carcinomas (14 recurrences out of 17 cases treated), and encouraging results in patients with carcinoma of the bladder (46 cases, with results apparently comparable to those obtained with classical fractioned irradiation).