Population-based sentinel lymph node biopsy in early invasive breast cancer.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) has been proposed as a reliable method for staging of early invasive breast cancer (EIBC). In the present study we analyse the impact of this procedure when systematically applied to all unselected women of a community-based Breast Cancer Unit (BCU). METHODS: All consecutive women with unifocal cT1-2 (

Sentinel node biopsy in the surgical management of breast cancer: experience in a general hospital with a dedicated surgical team.

The aims of this study were to analyse the feasibility and accuracy of the sentinel lymph node biopsy (SLNB) procedure as performed in a general hospital compared with the literature results; to report on the organizational aspects of planning surgical time with higher accuracy of pathological analysis; and to verify that there is a real advantage of SLNB in the surgical management of breast cancer. From October 1999 to September 2000, 371 consecutive patients with T1-2N0 breast lesions underwent SLNB. The immunoscintigraphic method of sentinel node identification was the main one used, the blue dye method being used only when the lymphoscintigraphic method was unsuccessful in identifying sentinel nodes. SLNB was done under either general or local anaesthesia, depending on how the surgical procedure was organized and clinically planned. SLNB was successful in 99% of these T1-2N0 breast cancer cases, and in 71% no metastases were found in the sentinel node. In 47% of cases with axillary metastasis only the sentinel node was involved. Nodal involvement was not present in any case of microinvasive or in situ carcinoma. In T1 cancers nodal involvement was present in 21%; in T2 cases the corresponding rate reached 51%. The results obtained with the SLNB procedure at Bergamo Hospital are similar to the literature data. When a dedicated surgical team, the nuclear medicine department and the pathology department work together, a general hospital can provide breast cancer patients with appropriate surgical treatment.

Electropotential measurements as a new diagnostic modality for breast cancer.

BACKGROUND: Proliferative changes in breast epithelium are an intrinsic aspect in the development of breast cancer, and result in regions of epithelial electrical depolarisation within the breast parenchyma, which can extend to the skin surface. Diagnostic information might be obtained from a non-imaging and non-invasive test based on skin-surface electropotentials. METHODS: In 661 women, scheduled for open biopsy at eight European centres, we studied whether measurements of breast electrical activity with surface sensors could distinguish benign from malignant breast disease. A depolarisation index was developed. RESULTS: We found a highly significant trend of progressive electrical changes according to the proliferative characteristics of the biopsied tissue. Discriminatory information was obtained in both premenopausal and postmenopausal women, and the index was not related to age. The best test performances were for women with palpable lesions. The median index was 0.398 for non-proliferative benign lesions, 0.531 for proliferative benign lesions, and 0.644 for cancer (ductal carcinoma-in-situ and invasive). A specificity of 55% was obtained at 90% sensitivity for women with palpable lesions when a discriminant based on age and the depolarisation index was used. INTERPRETATION: This new modality may have diagnostic value, especially in reducing the number of unnecessary diagnostic tests among women with inconclusive findings on physical examination. Understanding and control of the biological variability of these electrical phenomena will be important in the improvement of this test. Studies in populations with a lower cancer prevalence are needed to assess further the diagnostic value of this approach.

[Therapeutic alternatives in the treatment of class T1N0 squamous cell carcinoma of the penis: indications and limitations]. / Alternative terapeutiche nel trattamento del carcinoma spinocellulare del pene di categoria T1N0: indicazioni e limiti.

At INT of Milan between 1964 and 1990, 204 consecutive native patients suffering from penile cancer have been treated. 101 (59%) patients out of 171 with invasive cancer (23 affected with Tis were excluded) have been classified T1N0M0. 74 patients have been treated with penis conserving methods, such as circumcision, radiotherapy, laser excision and primary chemotherapy + conserving surgery. Overall local failure and/or nodal relapses occurred in 27% (20/74). Relapses are significantly related with grading but there isn't any relationship with macroscopical aspect or size of the tumor. The conservative treatment had been possible in 80% of patients. In our experience T1N0 clinical stage conservative therapy does not worsen the prognosis.

Results of a breast-cancer-surgery trial compared with observational data from routine practice.

BACKGROUND: The strength of randomised controlled trials (RCTs) is that they allow investigators to draw reliable inferences about treatment differences; physicians can then make a choice between different options. Their weakness is that they are conducted on a set of patients who cannot be regarded as a random sample from the population that will be treated outside the trial. Observational data collected in a prospective clinical database may provide more realistic estimates. METHODS: At the Istituto Nazionale de Tumori of Milan an RCT was started in 1973 (MI1) in which Halsted mastectomy was compared with quadrantectomy plus axillary dissection and radiotherapy (QUART), a breast conserving treatment, for "early-stage" primary breast cancer. In addition, a prospective clinical database was established to collect, in standard format, information on all women undergoing breast conservation thereafter and followed up at the Institute. 1760 women were treated with QUART, 350 of them being accrued in the years 1973-80 in the context of the MI1 trial. The remaining 1408 received QUART after the MI1 trial, up to December, 1984. RESULTS: In the years after the trial, the criteria for use of QUART became more liberal. However, after adjustment for baseline characteristics, out-trial patients fared no worse than trial patients in terms of survival or distant metastasis. Out-trial patients did have a slightly higher rate of local recurrence, probably because of subtle and multiple changes in the surgical procedures since the time of the trial. INTERPRETATION: The results of QUART in out-trial patients resembled those reported from research settings. In this instance, the results of clinical trials did not exaggerate the benefits obtainable in routine practice.

Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events.

BACKGROUND: Local disease recurrences are a concern in conservative breast cancer surgery, and many studies have attempted to identify risk factors for these events. It is important to distinguish local recurrences linked to increased risk of distant spread from those due to inadequate local treatment. PURPOSE: We evaluated the incidence of local and distant recurrences according to demographic, biological, and pathologic variables in a large series of women who were conservatively and uniformly treated for breast cancer, with the aim of identifying women in whom local failure is predictive for distant metastases and who are therefore candidates for aggressive systemic treatment. METHODS: Medical records of 2233 women who had been hospitalized at the Milan Cancer Institute from 1970 to 1987 were analyzed. All women received quadrantectomy and axillary lymph node dissection followed by radiotherapy for the breast. Quadrantectomy is breast-conserving removal of most of the affected quadrant by a radial incision that includes part of the skin. The end points considered were local failures (including local recurrences and new ipsilateral carcinomas) and distant metastases. Statistical analysis employed the competing risks and multiple failures approaches. RESULTS: There were 119 local recurrences, 32 new ipsilateral carcinomas, and 414 distant metastases as first events. The timing of local failures and distant metastases differed: The yearly probability for local failures was approximately 1% up to the 10th year and for distant metastases was 5% in the 2nd year and decreased progressively until the 8th year. Young age was an important risk factor, with peritumoral lymphatic invasion also predictive for local and distant recurrences. Tumor size and axillary lymph node involvement were not related to local recurrence but were important predictors of distant metastases. Extensive intraductal component was only a risk factor for local recurrence. Early (< 2 years) local failure predicted for distant metastases compared with later failure. In local failure patients, the 5-year survival rate was 69% from failure. CONCLUSIONS: Local recurrences and distant metastases are partially independent events that occur at different times; several predicting factors also differ. However, women with local recurrences have increased risk of distant metastases. In particular, women 35 years old or younger at first diagnosis who had initial peritumoral lymphatic invasion and local recurrence within 2 years are at high risk for distant spread. For recurrence in cases with an extensive intraductal component or where initial local surgery was possibly inadequate, women are at lower risk.

Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer.

Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses.

Effect of menstrual phase on surgical treatment of breast cancer.

1175 premenopausal women whose date of last menstrual period was known were followed up for up to 20 years (average 8 years) after surgery for breast cancer. 525 patients were in the follicular phase and 650 in the luteal phase. We observed 192 unfavourable events among patients operated on during the follicular phase (36.6%) and 192 among patients operated on during the luteal phase (29.6%). The effect of phase was restricted to patients with positive axillary nodes. The 5-year relapse-free survival was 75.5% in 246 node-positive patients operated on during the luteal phase and 63.3% in 190 node-positive patients who had surgery during the follicular phase. The hazard ratio at Cox multivariate analysis was 1.329 for all patients (p = 0.006) and 1.431 for node-positive patients (p = 0.03). In our study, premenopausal patients with breast cancer and positive axillary nodes operated on during the luteal phase had a significantly better prognosis than patients operated on during the follicular phase. It may be that the processes of cell metastases, such as loss of adhesiveness, may be enhanced by high concentrations of unopposed oestrogens or by reduced activity of natural killer cells during the first half of the menstrual cycle.

Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer.

At Istituto Tumori of Milano in a series of 3295 patients treated with conservative surgery and radiotherapy for breast cancer from 1973 to 1989 three cases of soft tissue sarcoma were observed in irradiated breasts. One patient developed a fibrosarcoma of the breast stroma, 16 months after irradiation. A grade II bulky angiosarcoma was diagnosed in the breast of a patient treated 59 months previously. The third was a grade II angiosarcoma detected 41 months after therapy. At present, the risk of a second primary in the irradiated breast seems too low to justify modification of our present policy of conservative therapy of breast cancer, but a careful and longer follow-up is needed.

Radiotherapy after breast-preserving surgery in women with localized cancer of the breast.

BACKGROUND AND METHODS: Conservative surgery and radiotherapy have become well-established treatments for breast cancer, and many trials in progress are attempting to define the most acceptable type of procedure. Between 1987 and 1989 we randomly assigned 567 women with small breast cancers (< 2.5 cm in diameter) to quadrantectomy followed by radiotherapy or to quadrantectomy without radiotherapy. All patients underwent total axillary dissection. The median follow-up period was 39 months (range, 28 to 54). RESULTS: The incidence of local recurrence was 8.8 percent among the patients treated with quadrantectomy without radiotherapy, as compared with 0.3 percent among those treated with postsurgical radiotherapy (P = 0.001). However, there was a substantial effect of age: patients more than 55 years old who did not receive radiotherapy had a low rate of local recurrence (3.8 percent). The four-year overall survival was similar in the two treatment groups. CONCLUSIONS: Administering radiotherapy after quadrantectomy reduces the risk of local recurrence in women with small cancers of the breast, but radiotherapy may not be necessary in elderly women.

Breast carcinoma presenting as axillary metastases without evidence of a primary tumor.

BACKGROUND: Sixty cases of axillary metastases from clinically occult breast cancer were analyzed. All cases had histologic evidence of metastatic nodes compatible with breast carcinoma. METHODS: Thirty-three patients underwent breast surgery at the time of histologic diagnosis of the axillary metastases, 6 patients were treated with radiation therapy to the breast, and 17 patients did not receive any immediate treatment of the breast carcinoma (9 of these subsequently had a primary breast carcinoma) during the follow-up. Thirty-seven of 60 patients underwent adjuvant therapy (29 underwent chemotherapy and 8 underwent tamoxifen therapy). From the histologic point of view, the number of metastatic nodes was 1 in 13 patients, 2 to 3 in 10 patients, and 4 or more in 23 patients; the number of metastatic nodes was not evaluable in 14 cases. Invasion was extranodal in 92% of cases. Eighty-six percent of cases were histologically classified as Grade 3 according to Bloom and Richardson. RESULTS: The 5-year and 10-year survival rates were 77% and 58%, respectively. The comparison between the survival curves of the patients treated with immediate surgery/radiation therapy and of the patients whose cases were followed-up without treatment to the breast showed no difference. Adjuvant treatments did not improve prognoses. CONCLUSIONS: The coexistence of a minimal (or unidentifiable) primary carcinoma with an extensive involvement of axillary nodes and a predominance of the undifferentiated histologic type, together with an unexpectedly good prognosis, makes this type of presentation an interesting example of a dissociated host resistance.

The preservation of minor pectoralis muscle in axillary dissection for breast cancer: functional and cosmetic evaluation.

We have evaluated, in two groups of 50 patients each submitted to axillary dissection for breast cancer (10 mastectomies and 90 conservative procedures), the advantage of the preservation of the minor pectoralis muscle. This muscle was preserved in one group and removed in the other. Whereas in the immediate postoperative period complications (shoulder pain, functional impairment, quantity or duration of serum drainage from the axilla) were the same in the two groups, at longer follow-up (more than 6 months after surgery) the patients whose pectoralis minor muscle was preserved showed a reduction in the incidence of partial atrophy and fibrosis of the pectoralis major muscle. Patients treated with conservation of the pectoralis minor muscle showed this atrophy in 6% of cases vs 54% observed in the other patients. This fact may be related to disruption of the pectoral nerves, which are in close contact with the pectoralis minor during their course from the brachial plexus to the pectoralis major muscle.

Quantitative and qualitative cosmetic evaluation after conservative treatment for breast cancer.

148 consecutive patients treated by two different types of conservative surgery were objectively and subjectively evaluated for cosmetic outcome. In 73 patients, tumorectomy, axillary dissection, external radiotherapy (45 Gy) plus iridium implant (15 Gy) were performed, while in the other group of 73 patients a more extensive surgical approach was carried out: quadrantectomy, axillary dissection plus external radiotherapy (50 + 10 Gy). The appearance of the patients' breasts was analysed for symmetry by computer, and differences in symmetry were correlated with tumour location and breast size. A subjective assessment was given by a 3-member panel and the results were correlated with objective measurements. In addition, patients were asked to fill out a self-assessment questionnaire on the aesthetic result of the operated breast. Better results were generally noted in the group of patients treated by more conservative surgery. Substantial differences in the aesthetic outcome were noted between the patient's own evaluation, the computer's measurement of symmetry and the assessment of the panel of observers.

Immunohistochemical study of ten cases of argyrophilic carcinoma (carcinoid) of the breast.

The significance of argyrophilia in human breast cancer is still a controversial issue. We tested immunohistochemically 10 cases of argyrophilic carcinomas of the breast and found evidence of immunoreactivity with neuroendocrine markers: chromogranin, NSE, gastrin, insulin and bombesin. Argyrophilia was demonstrated in breast cancers of the usual types and was found to be related to the secretory activity of neoplastic cells. Unfortunately, no adequate follow-up data are available to clarify the natural history of argyrophilic breast cancer. A clinical treatment different from that of conventional breast cancer is not at present justified.

Distribution of axillary node metastases by level of invasion. An analysis of 539 cases.

Five hundred and thirty-nine patients with carcinoma of the breast treated with total axillary dissection and with positive axillary nodes were evaluated. The total number of lymph nodes removed was 11,082, with an average of 20.5 nodes per patient. The average number of lymph nodes at the first level was 13.8, at the second level 4.5, at the third level 2.2. The average number of nodes was 20.7 in cases treated with Halsted mastectomy, 20.9 with total mastectomy and axillary dissection, 20.3 with quadrantectomy and axillary dissection. Of 3259 metastatic nodes, 64 were site of micrometastases; 797 were partially involved, 441 were totally involved and 1957 were site of metastases with extracapsular invasion. In 314 (58.2%) the first level only was involved, in 117 cases (21.7%) metastases were present at the first and second level, whereas in 88 cases (16.3%) all the three levels were sites of metastases. Only 20 cases showed skipping distribution. In 1.5% of the cases the first level was skipped by metastases, in 0.4% the first nodes of the first level are clear the chances that metastatic nodes are present at the second and third levels are negligible. When the nodes at the first level are positive, the chances that metastases are also present at the higher levels are of the order of 40.0%.

A reappraisal of oophorectomy in carcinoma of the breast.

Bilateral oophorectomy was used to treat 601 patients with disseminated breast carcinoma from 1974-1984. The total response rate was 31.2%. Complete regression occurred in 10.5% of patients and partial regression occurred in 20.8%, whereas 28.3% of patients showed no change and the disease progressed in 36.9% of patients. The patients who had a total regression had good survival rates (60.8% at 5 years and 47.3% at 7 years). No significant differences were found in the various age groups or with different types of dissemination. Patients with syncronous primary carcinoma and distant metastases had a high rate of regression as did patients with slow-growing carcinomas that metastasized many years after primary treatment. Estrogen receptor (ER) rates were good indicators of response only when determined on metastatic tissue at the time of oophorectomy. The value of ER determined on the primary tumor was of limited predictivity of response. A total of 220 patients received chemotherapy before oophorectomy. In this group the response rate was 22.3%, lower than that observed in patients who did not receive chemotherapy (36.6%). No important differences in total response rates were found among patients with amenorrhea and without amenorrhea although total regressions were more frequent in the latter patients than in the former patients.