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This paper reports findings of the "Focus on Controversial Areas" Working Party of the Italian Senonetwork, which was set up to improve the care of breast cancer patients. After reviewing articles in English on the MEDLINE system on breast conserving surgery for invasive carcinoma, the Working Party presents their recommendations for identifying risk factors for positive margins, suggests how to manage them so as to achieve the highest possible percentage of negative margins, and proposes standards for investigating resection margins and therapeutic approaches according to margin status. When margins are positive, approaches include re-excision, mastectomy, or, as second-line treatment, radiotherapy with a high boost dose. When margins are negative, boost administration and its dose depend on the risk of local recurrence, which is linked to biopathological tumor features and surgical margin width. Although margin status does not affect the choice of systemic therapy, it may delay the start of chemotherapy when further surgery is required.

Aims and Background: Anthracyclines such as doxorubicin play a central role in the management of advanced breast cancer. Unfortunately, the clinical benefits of anthracyclines are limited by cardiotoxicity that can lead to the development of potentially fatal congestive heart failure. In order to limit anthracycline-related cardiotoxicity, liposomal formulations of doxorubicin have been developed. This retrospective analysis evaluated the experience obtained with non-pegylated liposomal doxorubicin as first-line therapy in 34 patients with metastatic breast cancer., Methods: Patients received non-pegylated liposomal doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n = 20) for up to eight cycles, and efficacy and safety were assessed according to standard criteria., Results: The overall response rate was 71%. The median progression-free survival was 8 months in patients receiving non-pegylated liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly observed toxicities were grade 1-2 leucopenia, alopecia, nausea and vomiting; no grade 3-4 toxicities were observed. Overall, three patients (9%) experienced grade 1 cardiac toxicity., Conclusions: Our results support the use of non-pegylated liposomal doxorubicin as an alternative to conventional doxorubicin formulations in combination regimens for the first-line therapy of metastatic breast cancer.

Background: Axillary lymph node status is the most important pathological determinant of prognosis in early breast cancer. However, axillary lymph node dissection (ALND) performed for pathological assessment is not without costs and morbidity. Recently, radioisotope-guided sentinel node biopsy (SNB) has been proposed as a promising technique for staging breast cancer patients., Aim of the Study: In this study we report our experience (76 patients) in radioguided sentinel node (SN) biopsy in breast cancer. The study was divided into two phases: the first represents our learning curve, necessary to establish our guidelines for its use in clinical practice, while the second phase was aimed at assessing the feasibility of SN localization using preoperative lymphoscintigraphy and intraoperative gamma probe (GP) detection., Methods: All patients underwent lymphoscintigraphy (LS) up to two hours after tracer delivery (99mTc-micro-nanocolloid, four i.d. injections of 200 microCi/200 miccroL around the primary lesion) 24 hours before surgery and GP tracing during surgery. Subsequently ALND was performed for pathological assessment., Results: SNs were identified in 73/76 patients using LS and in 72/76 using GP. In one case the SN was detected by GP alone while in two cases GP was not able to locate the SN although it had been identified by means of LS. Thirty-three of these 73 patients had axillary node involvement. In 31/33 cases the SN was the only positive node. No positive nodes were found in the remaining 40 ALNDs where SNs were identified. Thus, according to our experience 40/73 ALNDs could have been avoided. SNB seems to be a very interesting technique but further experience in lymph node radioisotope tracing is needed.

Aims and Background: The association of p53 protein accumulation and prognosis in node-negative breast cancer patients has been alternately demonstrated and denied in literature reports, and opinions on the use of p53 expression as an indicator of high risk of recurrence and as a guide for adjuvant therapy are controversial., Study Design: The association of p53 protein accumulation with prognosis was retrospectively evaluated in a series of 221 node-negative breast cancer patients treated with surgery alone and followed up for a minimum of 10 years. p53 accumulation was determined by immunohistochemistry on archive material, and classified into four grades of increasing immunostaining., Results: No association was observed between p53 and age or pT category, whereas a significant association with nuclear grade was found (P = 0.0014). Univariate and multivariate analysis of 10-yr disease-free and overall survival showed a significant and independent prognostic association for tumor size (pT category) and nuclear grading but not for p53 expression, whatever grade grouping was used., Conclusions: We did not find any evidence supporting the use of p53 immunostaining in current practice as an independent prognostic indicator or as a discriminant factor for adjuvant treatment of node-negative breast cancer patients.

The authors report on a retrospective consecutive multicentric series of 60 cases with histologic evidence of lobular carcinoma in situ (LCIS), followed for an average of 5.3 years. In the course of the follow-up, ipsilateral LCIS or infiltrating carcinoma occurred in 3 or 5 cases, respectively. Two LCIS reoccurrences and all ipsilateral infiltrating carcinomas were observed in 37 patients treated by limited surgery. Contralateral synchronous or metachronous carcinoma was observed in 3 or 2 cases, respectively (intraductal = 3, infiltrating = 2). Three patients died of breast cancer (2 with ipsilateral, 1 with ipsilateral and contralateral infiltrating carcinoma). The study confirms the higher risk of ipsilateral and contralateral cancer in LCIS patients and warns about the possible hazards of limited surgery in these cases.

A multicenter series of 350 intraductal breast cancers (DCIS) is reported. Mammography was the most sensitive test but suspicion arose only at palpation in 13% of cases whereas in 10% of cases biopsy was recommended for a benign lesion and DCIS was an unexpected finding. Mammography, physical examination and cytology must be combined to achieve optimal sensitivity. Systematic biopsy of apparently benign masses would increase DCIS detection rates but the cost-effectiveness of such a policy is questionable. A trend of conservative surgery was evident over time (from 1968-79, 28%; 1985-1989, 50%) but breast irradiation followed only in one fourth of the cases. The local recurrence rate was significantly higher in cases of limited surgery (with or without irradiation) with respect to mastectomy (1.2 vs 0.2 x 100 patient-years at risk). Most recurrences (7 of 8) in the conserved breast were infiltrating, but no recurrence was seen in subclinical DCIS cases. Three patients died of breast cancer after local recurrence in the conserved breast (2 cases) or mastectomy scar (1 case). Eligibility for conservative surgery of DCIS needs to be carefully discussed to avoid under-treatment. Contralateral breast cancer was recorded in 44 cases and the incidence of further metachronous cancer to the other breast was ten times higher than expected in normal breasts. Four patients died of contralateral breast cancer, free of ipsilateral recurrence. A careful follow-up of the contralateral breast in DCIS cases looks as important as surveillance of the conserved breast.

The diagnostic role of physical examination (PE) is evaluated in 1450 cases of breast cancer detected in 34,677 women controlled at the Centro per lo Studio e la Prevenzione Oncologica in the period 1974-1981. In 47 cancer cases, PE findings were normal since the neoplasm was not clinically palpable because of its size and site, and in another 185 cases the clinical diagnosis was benignancy without evidence of suspect signs. Therefore, the overall sensitivity of PE was 84%. PE errors did not involve a therapeutic delay for the patient in 75% of cases in which a biopsy was recommended for clinical benignancy or for suspicion on the basis of other diagnostic methods. The present study confirms that PE has a good diagnostic sensitivity when the examined population is represented by self-referred women, who for the most part are symptomatic, whereas it cannot be considered as the only diagnostic test for early diagnosis in mass screening, since in asymptomatic women a large number of cancers are not clinically palpable. Moreover, PE shows lower sensitivity for small lesions and in younger women. Extensive use of fine needle aspiration cytology and other diagnostic methods in association with PE is therefore recommended to reduce the possibility of errors.

The authors report on 1,017 consecutive breast cancer cases without symptomatic metastases staged by means of chest X-ray (CXR), skeletal survey (BXR) and bone scintigraphy (BS). Occult metastases (DM) detection rate was 0.88%: 0.29% for lung and 0.59% for bone DM. The detection rate was correlated with clinical stage: 0.36% for stage I, 0.20% for stage II, 0.26% for stages I and II, and 2.77% for stage III cases. The sensitivity based on DM cases prevalent or surfacing within 6 months of follow-up was 0.30 for CXR, 0.22 for BXR and 0.55 for BS; specificity was 0.99, 0.98 and 0.90, respectively. The study confirms the possibility of early detection of DM with preoperative staging, but the extremely low detection rates in stage I and II cancers do not advise such a routine procedure. The higher detection rate of DM may suggest adoption of the routine staging procedure in stage III cancers. In these cases, although no evidence is available of a favorable prognostic impact of early detection and treatment of DM, an unnecessary mastectomy could be avoided in about 3% of cases in the presence of DM detected by the staging procedure.

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N- cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N- cases should be reconsidered.

The authors report on a consecutive series of 1979 TIS-T1A-T2A-T3A breast cancer cases surgically treated from 1979 to 1985. The study investigates the impact of recent reports on conservative surgery and of a national treatment protocol for breast cancer, encouraging the use of modified radical mastectomy (MRM) and quadrantectomy, axillary dissection and breast irradiation (QUART) as alternatives to Halsted's radical mastectomy (RM). RM frequency dropped from 52% to 8% in TIS-T1A and from 82% to 20% in T2A-T3A cases in the study period, in favor of MRM and of QUART, which increased from 10% to 54% in TIS-T1A cases. Although surgical choices differ widely according to individual surgeons, a definite trend towards more conservative surgery is evident, which demonstrates how the national treatment protocol has affected current surgical practice.