Brain metastases free survival differs between breast cancer subtypes.

BACKGROUND: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. METHODS: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). CONCLUSION: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.

Medium-term follow-up data after sentinel node biopsy alone for breast cancer.

AIMS: In patients with early breast cancer sentinel node biopsy (SNB) proved to be an accurate procedure for axillary staging with significantly reduced morbidity. Medium- and long-term observational studies are needed to establish, whether SNB alone is able to prevent locoregional recurrence without impairing long-term survival. METHODS: 298 patients with invasive breast cancer were subjected to SNB in a prospective audit. Lymphatic mapping was performed with blue dye and radiocolloids. 180 patients had SNB alone (group 1), while 118 subsequently underwent axillary dissection (AD; group 2). In ten patients AD was omitted despite the tumor burden in the SN. Clinical follow-up studies were performed at regular intervals. The mean follow-up time was 47months in group 1 (range 7-90) and 46months in group two (range 1-87months). RESULTS: Sentinel nodes were identified in 286 out of 298 patients (96%). One patient in group 1 developed axillary and simultaneous supraclavicular lymph node recurrence. After AD regional relapses have so far not been observed. One ipsilateral local recurrence was detected in each group. Five patients in group 1 and 15 patients in group 2 developed distant metastases. Three out of six and eight out of nine patients, respectively, died of their advanced disease. All patients with SN tumor infiltration not subjected to AD are alive and well. CONCLUSIONS: Axillary recurrence is rare after sentinel node biopsy alone. Its rate is comparable to that after AD, even in patients with SN micrometastases. These conclusions are confirmed by reports in the literature.

[Correlation of histology of the primary tumor with liver metastases in colorectal carcinoma]. / Beziehung zwischen der Histologie des Primärtumors und der Lebermetastasierung beim kolorektalen Karzinom.

The histology of colorectal tumors was correlated with the presence of liver metastases in a retrospective study performed on 179 patients who were autopsied between 1975 and 1990. For the analysis of metastatic patterns, 116 cases with at least one distant metastatic site were selected. A distinct relationship between mucin expression of colorectal tumors and liver involvement was found. Pure adenocarcinomas and their papillary variants showed the highest affinity to the hepatic tissue regarding the frequency as well as extent of involvement. A subtotal replacement of the liver by metastases was restricted to these two variants. An extracellular mucin component was associated with a lower frequency of liver involvement and a tendency to solitary or oligotopic metastases. Ten cases of signet ring cell carcinomas had no metastases in the liver. The results described here for colorectal cancers are similar to those previously reported for gastric cancer. The therapeutic implications were discussed. A detailed link between these clinical findings and the results found at the level of molecular biology is yet to be determined.

Malignant prolactinoma: case report and review of the literature.

BACKGROUND: Malignant prolactinomas are rare events. To date, only 14 patients with metastases in- or outside the central nervous system have been reported. CASE DESCRIPTION: We present a patient who developed a metastasis to the cauda equina, which is the first case documented with MRI. A giant prolactinoma in this 51-year-old man was partially removed by a transcranial approach. After radiotherapy and treatment with bromocriptine, the patient had a remission for 3 years. Thereafter, a sacral intraspinal tumor was diagnosed. Because of increasing prolactin levels not responding to bromocriptine and a radiologically suspected intrasellar tumor, we operated transsphenoidally first and found only fibrous tissue. We performed a sacral laminectomy and almost totally removed an intradural tumor. Histopathology and immunohistochemistry confirmed the diagnosis of a prolactinoma metastasis. The patient received radiotherapy and bromocriptine and has no evidence of recurrent tumor or metastases after a follow-up of 38 months, thus being the second reported patient with long-term remission of the disease. DISCUSSION: We review the literature on this topic and try to establish common features of the course of this rare malignant disease and the efficacy of therapy in the cases reported hitherto.

[Malignant hemangioendothelioma of the thyroid gland: new results on pathogenesis, therapy and prognosis]. / Das maligne Hämangioendotheliom der Schilddrüse: Neue Resultate zur Pathogenese, Therapie und Prognose.

BACKGROUND: Malignant hemangioendothelioma of the thyroid is a rare tumor predominantly described in areas with endemic goiter like the Alpine regions. The estimated incidence of the disease is between 0.15 and 0.25 per 100,000 inhabitants per year for Western Austria. The prognosis is reported to be dismal. MATERIALS AND METHODS: Between 1982 and 1995, 10 cases with immunohistochemically confirmed malignant hemangioendotheliomas of the thyroid were referred to our department for postoperative or palliative treatment. Two patients with clear margins at surgery received no adjuvant radiotherapy and were only observed. By surgery, clear margins (R-0 resection) were achieved in 5, microscopic residuals (R-1) were left in 3, and gross residual disease in 1 patient. One patient had an inoperable primary tumor. Postoperative radiotherapy was administered in 6 cases, 4 of them additionally received the radiosensitizer razoxane. Total tumor doses ranged between 58 and 65 Gy. RESULTS: Local tumor control was achieved in 9 of 10 patients; 4 of 10 lived longer than 4 years. The median survival time has not yet been reached and is presently between 7.5 and 21+ months.--Noteworthy is a complete regression of 2 lung metastases in a 72-year-old man by a combination of vindesine, razoxane and radiotherapy. The patient is still in complete remission under a maintenance therapy with vindesine and razoxane since 14 months.--It may also be of interest that 4 of the 10 patients were strongly exposed to vinyl chloride and other polymeric materials during their occupational life. CONCLUSIONS: This small series may indicate that the outcome of this disease may not be uniformly deleterious, and that the resistance to radiotherapy reported in the literature may be questioned.--The data offer new evidence of the occurrence of vinyl chloride-induced angiosarcomas outside the liver, and support observations which have already been published in case reports.

[Is axillary dissection in clinically lymph node-negative breast carcinoma further indicated?]. / Ist die Axilladissektion beim klinisch nodal negativen Mammakarzinom weiter indiziert?

BACKGROUND: In the treatment of breast cancer, the indication for adjuvant systemic treatment was extended also to nodal negative tumor stages in the last years. For that reason, the indicator status of axillary dissection lost some of its importance. Therefore, in node negative patients, the necessity of axillary dissection and the use of definitive axillary radiotherapy, which causes less morbidity, may be reconsidered. METHODS: In a review of the related literature, we present international treatment experiences related to axillary dissection, axillary radiotherapy and "sentinel node dissection" (SLND). In addition, our long-term experiences in 19 patients with clinically negative axillary nodes treated by conservative surgery without axillary dissection but axillary radiotherapy, are reported. RESULTS: The median rate of axillary recurrences with axillary radiotherapy is 2.0%, the regional (supraclavicular and retrosternal) recurrence rate 2.7%. With axillary dissection, axillary recurrences occur in 1 to 2%, in nodal negative stages in 0 to 1%, the median regional recurrence rate is 2.2%. A meta-analysis presented in 1995 by the Early Breast Cancer Study Group showed no significant difference in the regional recurrence rate or the overall survival between axillary dissection and axillary radiotherapy. With SLND, usually only one axillary node is excised. With the help of molecular and immunohistochemical methods, SLND may predict axillary involvement with high precision. CONCLUSIONS: Definitive radiotherapy of the axilla is a valid treatment option for patients without palpable axillary nodes with the potential advantage of being less cost intensive and better tolerated. If the indication for systemic therapy is no more dependent on the axillary status, axillary dissection may be replaced by axillary radiotherapy. In small tumors without risk factors and without indication for systemic therapy, SLND seems to be the best treatment option.

Inoperable recurrent rectal cancer: results of a prospective trial with radiation therapy and razoxane.

PURPOSE: The effect of the sensitizer razoxane was prospectively evaluated in recurrent rectal cancer. Endpoints of the study were mainly local response rates and survival. METHODS AND MATERIALS: From 1984 to 1990 razoxane was given together with radiation therapy to 40 patients with recurrent inoperable rectal cancer. Loco-regional relapses in the pelvis were isolated in 24 and associated with distant metastases in 16 patients. Special attention was given to the subset of 24 patients with isolated local recurrences. This group was compared with historical controls treated with radiotherapy alone. The dosage of razoxane was 150 mg/m2 daily orally starting 5 days before the first irradiation. The drug was then given each radiation day until the end of treatment. The median radiation dose was 60 (40-62) Gy in the evaluable patients. The minimum follow-up was 32 months and the median 72 months. RESULTS: The rates of complete plus partial responses were 57% and 54%, respectively, for recurrent patients without and with distant metastasis. The 23 evaluable patients with isolated local relapses had a median survival of 24 months (12-94+); all patients surviving at least 1 year. CONCLUSION: The combination of radiotherapy and razoxane may lead to better local control and improved median survival compared to our historical controls and literature reports where radiotherapy alone was used. The treatment is easy to administer and is associated with a moderate toxicity.

[Prognosis and epidemiology of malignant hemangioendotheliomas of the thyroid gland]. / Zur Prognose und Epidemiologie des malignen Hämangio-endothelioms der Schilddrüse.

Five new cases of malignant hemangioendothelioma of the thyroid are reported. This rare malignant tumor is described predominantly in regions with endemic goiter such as the Alpine zone. The estimated incidence of the disease is between 0.15 and 0.25 per 100,000 inhabitants per year for Western Austria. Two of the five patients were heavily exposed to vinyl chloride occupationally for 9 and 30 years respectively. Surgically, a R-0 resection was performed in two patients, R-1 in two, and R-2 in one patient. Postoperative radiotherapy was given in four cases. The tumor doses were between 58 and 65 Gy. Three patients received the sensitizer razoxane in addition. Local tumor control was achieved in 4 of 5 patients. The survival times of the 5 patients were 78, 68+, 38+, 7.5 and 3 months. Two patients are still alive after 68 and 38 months. This small series may indicate that the outcome of the disease may not be uniformly deleterious and the resistance to radiotherapy reported in the literature [3, 10] is debatable.

[Radio-oncological treatment possibilities in local recurrence of rectal carcinoma. An interdisciplinary comparison]. / Radioonkologische Behandlungschancen beim Lokalrezidiv des Rektumkarzinoms. Ein interdisziplinärer Vergleich.

Local recurrences of rectal carcinomas are frequently associated with a considerable morbidity and a dismal prognosis. Surgical resection leads to long term tumor control in about 30 to 40%, but surgery can be offered to only 10 to 30% of the patients. Cytotoxic chemotherapy is able to induce local responses in 15 to 40% of the cases--similar figures as achieved by radiation therapy alone. A pilot study is presented using radiation therapy combined with the sensitizing agent razoxane (ICRF 159). There was an objective response rate of 62% and the median survival rose to 24 months (13 months with radiation therapy alone). These data compare almost to results seen in surgical series. However, they need confirmation.

Long-term application of vindesine: toxicity and tolerance.

This is a report on 14 patients receiving vindesine continuously for between 1 and 7 years. Total vindesine doses ranged from 86 mg to 454 mg and the longest treatment duration was 2564 days. Although there was no patient without a transient acute or subacute toxicity, no unequivocal signs of long-term toxicity have been observed so far. Greater caution must be given to the concomitant use of higher radiation doses and vindesine, since local reactions were more pronounced especially at the lung. The drug seems to be tolerated for longer periods without major or cumulative toxicity, which makes it suitable for use in the adjuvant setting, for instance, or within an antimetastatic approach.

[Radiation sensitivity studies of inoperable and recurrent rectal carcinomas]. / Studien zur Strahlensensibilität inoperabler und rezidivierender Rektumkarzinome.

Two pilot studies on the radiosensitivity of rectum carcinomas have been conducted, during which 42 patients with inoperable primary tumors or recurrences were irradiated with focal doses of about 60 Gy. A rate of 38% of objective remissions was observed under conventional telecobalt irradiation, 20% were progressing in spite of radiotherapy. In case of simultaneous peroral administration of razoxane, an objective remission rate of 67% was observed, and none of the tumors was progressing during or immediately after radiotherapy. Remissions were found most frequently in inoperable primary tumors and anastomotic recurrences. The radiosensitivity of the recurrent rectum carcinoma has to be considered as only fairly good. Nevertheless, local recurrences without remote metastases should always be treated by radiotherapy, because a much better median survival time and quality of life can be achieved than by a mere symptomatic therapy.

[Radiation-induced vaginal necrosis]. / Strahlenbedingte Vaginalnekrosen.

A report is given on three cases of total vaginal necrosis observed between 1980 and 1983 in 156 evaluable patients submitted to primary or postoperative irradiation. Characteristic signs of this disease are the incidence of sudden pains (increased in sitting position), necrosis and ulceration of the complete vaginal area, and a tendency to spontaneous recovery. All patients had been treated by hysterectomy or Wertheim operation, suffered from associated cardiovascular troubles, and had been exposed to a large surface irradiation of the vagina with 75 to 90 Gy. The disease was reversible in two cases, one patient presented a rectovaginal fistula after a latency of three years. Further risk factors for this complication communicated in literature as well as the differential diagnosis of recurrent carcinoma are discussed.

[Cancer of the so-called "empty breast" and its relation to Wolfe's classification of parenchymal patterns]. / Das Karzinom der sogenannten leeren Brust und seine Beziehungen zur Klassifikation der Parenchymmuster nach Wolfe.

Carcinoma in the 'empty breast' in our experience is so common that we doubt Wolfe's conclusions in his classification of parenchymal patterns. Amongst patients over 60 years, almost 70% of carcinomas were situated in an 'empty' parenchyma and they did not develop in a parenchymal group above P1. Mammographically, the 'empty breast' is the structureless fatty breast of older women after the menopause. Some authors believe that there is a lower incidence of carcinomas in this type of breast than in other types of parenchyma, such as those showing mastopathies. Our experience concerning carcinomas in involuted breasts is described.