Prognosis of patients with local recurrence after mastectomy or conservative surgery for early-stage invasive breast cancer.

Between 1983 and 1987, 1309 women with stage I or II breast cancer underwent mastectomy (n=894) or conservative surgery (CS, n=415). Of these patients, 124 developed an isolated local recurrence (ILR): chest wall, 56 and in-breast, 68. The 10-year actuarial rate of cause-specific survival after treatment for ILR was 52%. On multivariate analysis three independent prognostic factors for the risk of death after ILR were identified: operability of recurrence (operable vs. inoperable, relative risk [RR]: 5.9), age at initial diagnosis (>40 vs. < or = 40 years, RR: 2.2) and time to ILR (>24 vs. < or = 24 months, RR: 2). Initial lymph node stage (negative vs. positive) showed borderline significance (p=0.06), and type of initial surgery (CS vs. mastectomy) and recurrent tumor grade (1-2 vs. 3) were not independent predictors of survival. In the mastectomy group, single surgical scar recurrence with initial node negative stage predicted good prognosis, and the 10-year survival was 85%. In the CS group, the 10-year survival rate was 88% with new primary tumor and 54% with true recurrence (p=0.01), and the type of salvage surgery (mastectomy vs. repeat complete excision) had no significant impact on survival (p=0.2). The majority (n=44) of CS patients developed < or = 2 cm in-breast recurrence, and the 10-year survival was 81% after both salvage excision (n=28) and mastectomy (n=16). The identified unfavorable prognostic factors are pointers of the forthcoming systemic progression. Patients with < or = 2 cm in-breast recurrence might receive a second CS.

[Breast-conserving treatment for early invasive lobular breast cancer: 15 years results]. / Emlómegtartó kezelés korai invazív lobularis emlórákban: 15 éves eredmények.

BACKGROUND: Infiltrating lobular cancer is biologically different from invasive ductal cancer and there is disagreement regarding appropriate local management of this disease. PURPOSE: To examine treatment outcomes after breast-saving surgery for patients with invasive lobular breast cancer. MATERIAL AND METHODS: Between 1983 and 1987, 77 women with early, stage I-II invasive lobular breast cancer were treated with complete gross excision of the tumour and axillary dissection. Fifty-eight of these patients were treated with 50 Gy ipsilateral breast irradiation, and 19 did not receive radiotherapy. During 176 month median follow-up local-regional recurrences, distant metastases, contralateral breast cancers, breast cancer deaths and deaths caused by other disease were scored. The probability of survival was estimated by Kaplan-Meier method. In uni- and multivariate analysis the Cox-model was used. Relative risk (RR) and associated confidence intervals (CI) were calculated from the regression coefficients. Statistical differences in proportions and means were assessed by log rank and Fisher exact-tests. RESULTS: In the saved breast, the actual rate of local recurrence at 15 years was 13% for irradiated and 53% for non-irradiated patients (RR: 0.1; 95% CI: 0.03-0.31; p: < 0.0001). The incidence of total breast cancer relapses (local-regional recurrences and distant metastases) was also higher for non-irradiated than for irradiated patients (74% vs. 40%; p: 0.0168). In multivariate analysis irradiation (no vs. yes) showed a significant effect on local tumour control (RR: 0.08: 95% CI: 0.02-0.28; p: 0.0001), but menopausal (pre vs. post), T-(T1 vs. T2) and N-(N0 vs. N1) status did not. The breast cancer specific survival at 15 years was 74% without and 62% with local recurrence (RR: 1.45; 95% CI: 0.53-3.96; p: 0.4697). The majority of local recurrences (9 of 14) were curable by salvage surgery. For all patients the rate of contralateral breast cancer was 6.5%. CONCLUSION: Results of long-term follow-up confirmed that breast-conserving surgery and radiotherapy is a reasonable treatment for patients with early invasive lobular breast cancer. The majority of local recurrences are curable by salvage surgery.

Characteristics of cystic breast disease with special regard to breast cancer development.

BACKGROUND: This prospective study compares the characteristics of cystic disease of the breast (CDB) of patients who developed breast cancer (BCa) during the follow-up (1.25-4 years) period with those who did not. MATERIALS AND METHODS: K+, Na+, albumin, dehydroepiandrosterone (DHA), DHA-sulphate, oestrone, oestradiol, testosterone and progesterone levels were determined in breast cyst fluid (BCF). Patients presented data about their menstrual status, reproductive history, lactation period, date of first and the number of BCF aspirations, gynaecological interventions, use of oral contraceptives, family history of cancer, smoking habits and coffee consumption. The BCa incidence of patients was compared with the expected number of BCas in an age-matched group of 5143 women. RESULTS: Out of 147 patients 6 developed BCa. The standardized incidence rate was 6.29. There were significant differences in testosterone, oestrone and progesterone levels and also reproductive history of patients who developed BCa compared with patients without BCa. CONCLUSION: The above markers outline a subgroup of patients with the highest BCa risk.

[Oncocytic carcinoid tumor of the lung]. / Tüdó oncocyter carcinoid tumora.

An elderly female patient was admitted and operated on for a lesion in the upper lobe of the right lung. After lobectomy the patient has recovered without complications. Histology proved oncocyter carcinoid tumour. This neuro-endocrine tumour is a rarity in the lungs with less than forty cases reported in the reviewed literature. This is the first case reported in Hungary.

[The effect of tumour bed boost on local control after breast conserving surgery. First results of the randomized boost trial of the National Institute of Oncology] / A tumorágy kiegészítô besugárzásának hatása a lokális daganatmentességre emlômegtartó mûtét után. First results of the randomized boost trial of the National Institute of Oncology.

PURPOSE: To evaluate the effect of tumour bed boost on local tumour control (LTC) after breast conserving surgery in a prospective study. METHODS: Between 1995 and 1998, 207 women with early invasive breast cancer who underwent conservative operation were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either no further radiotherapy (n=103) or a boost to the tumour bed (n=104) with either 16 Gy electron (n=52) or 12-14.25 Gy high dose rate brachytherapy (n=52). RESULTS: At a median follow-up of 4.25 years the crude rate of local recurrence was 6.7% with and 13.6% without boost. The respective rates of tumour bed relapse were 3.8% vs. 10.7%. The 4 year probability of LTC, relapse-free survival and breast cancer-specific survival was 94.2% vs. 85.1% (p=0.1176), 82.3% vs. 67.2% (p=0.0438) and 84.8% vs. 90.9% (p=0.1111), respectively, in favour of the boost group. Systemic treatments had no significant impact on LTC (88.9% with and 89.6% without systemic treatment, p=0.8858). CONCLUSION: Tumour bed boost decreased the incidence of local and tumor bed relapses with a reduction of 50% and 64%, respectively. Relapse-free survival was improved significantly with boost. However, the influence of boost treatment on breast cancer-specific survival should be tested in further studies. In spite of the higher incidence of late radiation side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. The final results of the EORTC trial and other ongoing studies will help to clarify the indication of boost dose according to prognostic subgroups.

CT-image-based conformal brachytherapy of breast cancer. The significance of semi-3-D and 3-D treatment planning.

PURPOSE: To compare the conventional 2-D, the simulator-guided semi-3-D and the recently developed CT-guided 3-D brachytherapy treatment planning in the interstitial radiotherapy of breast cancer. PATIENTS AND METHODS: In 103 patients with T1-2, N0-1 breast cancer the tumor bed was clipped during breast conserving surgery. Fifty-two of them received boost brachytherapy after 46 to 50 Gy teletherapy and 51 patients were treated with brachytherapy alone via flexible implant tubes. Single, double and triple plane implant was used in 6, 89 and 8 cases, respectively. The dose of boost brachytherapy and sole brachytherapy prescribed to dose reference points was 3 times 4.75 Gy and 7 times 5.2 Gy, respectively. The positions of dose reference points varied according to the level (2-D, semi-3-D and 3-D) of treatment planning performed. The treatment planning was based on the 3-D reconstruction of the surgical clips, implant tubes and skin points. In all cases the implantations were planned with a semi-3-D technique aided by simulator. In 10 cases a recently developed CT-guided 3-D planning system was used. The semi-3-D and 3-D treatment plans were compared to hypothetical 2-D plans using dose-volume histograms and dose non-uniformity ratios. The values of mean central dose, mean skin dose, minimal clip dose, proportion of underdosaged clips and mean target surface dose were evaluated. The accuracy of tumor bed localization and the conformity of planning target volume and treated volume were also analyzed in each technique. RESULTS: With the help of conformal semi-3-D and 3-D brachytherapy planning we could define reference dose points, active source positions and dwell times individually. This technique decreased the mean skin dose with 22.2% and reduced the possibility of geographical miss. We could achieve the best conformity between the planning target volume and the treated volume with the CT-image based 3-D treatment planning, at the cost of worse dose homogeneity. The mean treated volume was reduced by 25.1% with semi-3-D planning, however, it was increased by 16.2% with 3-D planning, compared to the 2-D planning. CONCLUSION: The application of clips into the tumor bed and the conformal (semi-3-D and 3-D) planning help to avoid geographical miss. CT is suitable for 3-D brachytherapy planning. Better local control with less side effects might be achieved with these new techniques. Conformal 3-D brachytherapy calls for new treatment planning concepts, taking the irregular 3-D shape of the target volume into account. The routine clinical application of image-based 3-D brachytherapy is a real aim in the very close future.

Influence of hormonal status of patients with cystic disease on the composition of cyst fluid and breast cancer risk.

The relationship between the composition of breast cyst fluid (BCF), the menstrual status and in addition some endocrine events in the history of patients (n = 131) with gross cystic breast disease was investigated. The dehydroepiandrosterone (DHA) levels in type II (K+/Na+ < 1) cysts of the follicular group were significantly higher compared to the type II cysts of the luteal or postmenopausal groups. For testosterone a significant difference existed between the type I (K+/Na+ > or = 1) follicular and type I postmenopausal groups. Estrone levels were significantly higher in type I BCF of patients in the luteal phase compared to both the follicular and postmenopausal type I cysts. Progesterone levels were lowest in the postmenopausal subgroups (both in type I and II cyst). Significant correlations were found between the number of pregnancies and the levels of DHA-sulfate and also progesterone in BCF. DHA levels were correlated with the period of lactation. The K+/Na+ ratios were the lowest in women who lactated for the longest period. The estrone was lowest in BCF of current oral contraceptive (o.c.) users while the estradiol was lowest in patients who had never used o.c. A history of previous o.c. use was associated with a significantly high mean DHA level. A significantly higher DHA and lower testosterone level were demonstrated in BCF of patients who had some previous gynecological interventions. The composition of BCF and the "life of cysts" and thus the rate of breast cancer risk may depend on hormonal status during the menstrual cycles or postmenopause and also on endocrine history of patients.

[Reexcision and perioperative brachytherapy in the treatment of local relapse after breast conservation: a possible alternative to mastectomy]. / Reexcízió és perioperatív brachyterápia az emlómegtartó mútét utáni lokális recidíva kezelésére: a mastectomia lehetséges alternatívája.

Breast conserving surgery and postoperative radiotherapy became widely accepted in the last two decades for the treatment of early invasive breast cancer. In spite of adequate surgery and radiotherapy, the rate of ipsilateral breast tumor recurrence is approximately 10%. In such cases salvage mastectomy is the standard treatment, however wide reexcision of the recurrent tumor is also a reasonable option for selected patients. The risk of second local relapse is higher following further breast conservation compared to mastectomy. The authors report the technique of tumor reexcision combined with intraoperative implantation and perioperative high dose rate (HDR) bracytherapy of the tumor bed for the salvage of recurrence in a previously irradiated breast. One can perform two operative interventions at the same time with this method. Irradiation can be started safely within 48 hours after surgery. A review of the literature is also performed by the authors to demonstrate the role and indication of perioperative brachytherapy in the treatment of breast tumor relapse and other cancer recurrences. Reexcision is a practicable alternative to mastectomy for solitary, parenchymal breast tumor relapse measured 2 cm or less in diameter. Perioperative brachytherapy may decrease the risk of second relapse without increasing radiation side effects. Further prospective study is required to define the value of the prescribed method in comparison with salvage mastectomy.

Sole brachytherapy of the tumor bed after breast conserving surgery: a new radiotherapeutic strategy for patients at low risk of local relapse.

The aim of the study was to test the hypothesis, if there were subgroups of early breast cancer patients in which sole brachytherapy (BT) of the tumor bed was a feasible and safe treatment option after breast conserving surgery (BCS). Forty four prospectively selected patients with Stage I-II breast cancer were entered into a protocol of postoperative tumor bed irradiation using interstitial high dose rate (HDR) implants. The HDR fractionation schedules were calculated according to the linear quadratic model. In 8 patients 7 x 4.33 Gy, in the other 36 patients 7 x 5.2 Gy were delivered to the tumor bed with 2 cm margin. The treatment planning was based on the 3 dimensional (3D) reconstruction of the clipped excision cavity, catheters and skin points. A conformal semi-3D dose planning was used. The side effects were assessed by mammograms, MRI- and clinical examinations. At a median follow up of 20 (7-36) months 1 (2.3%) local and 1 (2.3%) regional failure was observed. Distant metastasis did not occur. The cosmetic results were judged to be excellent in each case. G2 radiation side effects were observed in 2 (4.5%) cases. Postoperative sole BT of the tumor bed with careful patient selection and adequate quality assurance seems to be a feasible alternative to whole breast radiotherapy after BCS. Sole BT shortens the time of radiotherapy from 5-6 weeks to 5 days, and reduces the costs of treatment. The skin and volume sparing effect of interstitial irradiation may decrease the side effects of radiotherapy. A randomized study is in progress to define which subgroups of patients should be candidates for BT alone after BCS.

[Brachytherapy of the tumor bed after breast conserving surgery: new radiotherapeutic option in the management of early breast cancer]. / A tumorágy egyedüli brachyterápiája emlömegtartó mütét után: új sugárterápiás lehetöség a korai emlörák kezelésében.

PURPOSE: To initiate fractionated, interstitial high dose rate brachytherapy of the tumour bed as the sole radiation modality after breast conserving surgery. PATIENTS AND METHODS: In 41 cases of selected stage I-II breast cancer the tumour bed was marked with titanium clips during breast conserving surgery. The tumour bed was implanted with flexible plastic catheters to deliver postoperative radiotherapy. In 8 cases 7 x 4.33 Gy (30.3 Gy), in 33 cases 7 x 5.2 Gy (36.4 Gy) interstitial 192Ir high dose rate brachytherapy was given to the clipped area. Irradiation of the whole conserved breast was omitted. The radiation side effects were assessed by mammograms and MRI-examinations. RESULTS: At a median follow up of 17 (4-36) months neither distant nor regional failure was observed. Local recurrence was detected in 1/41 (2.4%) case. G2 radiation side effects were observed in 2/21 (9.5%). CONCLUSIONS: Postoperative sole brachytherapy of the tumour bed with careful patient selection and adequate quality assurance seems to be a feasible alternative to whole breast teletherapy. Sole brachytherapy shortens the time of radiotherapy from 5-6 weeks to 5 days, and reduces the costs of treatment. The skin and volume sparing effect of interstitial irradiation may decrease the side effects of radiotherapy.

High frequency of germ-line BRCA2 mutations among Hungarian male breast cancer patients without family history.

To determine the contribution of BRCA1 and BRCA2 mutations to the pathogenesis of male breast cancer in Hungary, the country with the highest male breast cancer mortality rates in continental Europe, a series of 18 male breast cancer patients and three patients with gynecomastia was analyzed for germ-line mutations in both BRCA1 and BRCA2. Although no germ-line BRCA1 mutation was observed, 6 of the 18 male breast cancer cases (33%) carried truncating mutations in the BRCA2 gene. Unexpectedly, none of them reported a family history for breast/ovarian cancer. Four of six truncating mutations were novel, and two mutations were recurrent. Four patients (22%) had a family history of breast/ovarian cancer in at least one first- or second-degree relative; however, no BRCA2 mutation was identified among them. No mutation was identified in either of the genes in the gynecomastias. These results provide evidence for a strong genetic component of male breast cancer in Hungary.

Male breast tumours.

The data of 63 male breast cancer patients treated between 1967 and 1990 in the Department of Surgery of the National Institute of Oncology are described. Beside the 59 breast cancer cases four tumours of other histologic type were also detected. As to surgical treatment, in addition to mastectomy, the axillary block dissection is regarded as important in each case. The prognosis is mainly determined by the time elapsed until treatment and by the lymph node status. The mean survival of the axillary node negative patients was 116 months, compared to that of 38.9 months found in axillary node positive cases. Metastases were the soonest detected 2 years following surgery, altogether in 36 cases (61%). Local recurrence developed in eight patients (14%). Steroid hormone receptor investigations have been performed since 1980; of the 27 patients examined estrogen receptor positivity was seen in 25 cases. The hormone receptor study of the tumour and the assessment of the hormonal status of the patient provide valuable information for the treatment. In case of tumour progression the life of the patient might considerably be prolonged by combined hormone and cytostatic therapy.

[Breast-preserving operations in surgically treatable breast cancer]. / Szervmegtartásos mütétek operábilis emlörákban.

Since 1980, based on international experience, breast conserving operations have been introduced at the Surgical Department, in the National Oncological Institute, Budapest. In 12 years, out of 4622 primary breast cancer operations, 1055 breast preserving interventions were carried out. For all patients adjuvant radiotherapy was indicated. In lymph node positive premenopausal cases chemo-radio-chemotherapy, for postmenopausal patients radiotherapy with tamoxifen has been provided. The first 604 patients (10 years) have been evaluated and 489 of them could be followed. The mean follow-up time was 49 months. During this period of time metastases have developed in 61 patients (12.5%); 26 (5.3%) of them died with the disease. Local recurrences occurred in 29 patients (5.9%). For small recurrences reexcision, for the others mastectomy or/and radiotherapy was carried out. Critical evaluation of the local recurrences was done.

[Leiomyosarcoma in the male breast]. / Leiomyosarcoma férfi emlöben.

Leiomyosarcoma of a 61 y.o. male's breast was removed by the authors. This observation is the first in the Hungarian and third in the world literature. Short survey is taken of the aetiology, prognosis and therapeutic possibilities of male breast cancers.

[Malignant fibrous histiocytoma of the breast]. / Malignus fibrosus histiocytoma az emlöben.

In connection with the mammary tumor of a 41-year-old woman the authors draw attention to the rare occurrence of malignant fibrous histiocytoma in the mamma. The histology of the mammary malignant fibrous histiocytoma, role of immunohistochemical reactions in the diagnosis are described. The literature dealing with the malignant fibrous histiocytoma in the mamma is reviewed. This is the 11th case reported in the literature. The authors discuss the possibilities of the therapy of the malignant fibrous histiocytoma in the mamma.

Treatment of breast cancer in women older than 70 years.

Do age, associated diseases, general state, or the stage of tumor determine the operability of breast cancer in the elderly? Risk factors are studied on the basis of data on 465 patients over 70 years of age who had breast cancer surgery between 1977 and 1986. Operative mortality of patients is analyzed, and according to the results, the outcome of the surgery is mainly influenced by patients' performance status (Karnofsky/Zubrod index) and stage of disease and not by the associated diseases or patient age.