Rosaria Bufalino

Prognosis of breast cancer patients after mastectomy and dissection of internal mammary nodes.

The results of the analysis carried out on data on 1119 patients with operable breast cancer treated at the National Cancer Institute of Milan from 1965 to 1979 with enlarged mastectomy are reported. Metastases to internal mammary chain were found to be significantly associated with the maximum diameter of primary (16.1% for tumors less than 2 cm and 24.5% for larger tumors, p = 0.007), the age of the patients (27.6% in patients younger than 40 years, 19.7% in patients between 41-50 years, and 15.6% in patients older than 50 years, p = 0.01). The site of origin of the cancer had no impact on internal mammary node metastases. Patients with positive axillary nodes showed metastases to internal mammary nodes in 29.1% of the cases, while 9.1% of patients with axillary negative nodes had positive retrosternal nodes. Survival was significantly affected by the presence of positive internal mammary nodes: the percentage of 10-year survival varied from 80.4% in patients with axillary and internal mammary negative nodes to 30.0% in patients with both nodal basins involved. Intermediate survival rates (54.6% and 53.0%) were found when one or the other of the nodal stations (axillary and internal mammary) was separately affected. Maximum diameter of the primary significantly affected the survival of each group identified by the status of both axillary and internal mammary nodes. In conclusion, the information on the presence or absence of internal mammary node metastases would be of great importance in formulating the prognosis of breast cancer patients. To obtain this information, a biopsy at the first intercostal space may be reasonable in selected patients (age, maximum diameter, and axillary node involvement being the basis for selection) as long as noninvasive methods of diagnosis are available.

Risk of internal mammary lymph node metastases and its relevance on prognosis of breast cancer patients.

The risk of internal mammary chain metastases according to some parameters and its prognostic relevance was evaluated on the basis of the experience collected at the National Cancer Institute of Milan where, from January 1965 to December 1980, 1085 patients were submitted to Halsted mastectomy plus internal mammary chain dissection. A multivariate analysis was carried out, resorting to a multiple linear regression with logistic transformation of the dependent variable. The selection of prognostic factors has been performed with a step-down approach. The frequency of metastases to internal mammary chain nodes was evaluated according to four criteria: age, site and size of primary tumor, and presence of axillary metastases. Data of this series indicate that the frequency of internal mammary node metastases is significantly associated with the age of the patients (younger patients have a higher risk) (p = 0.006) with the size of primary tumor (p = 0.006) with the presence of axillary node metastases (p = 10-9). Patients with both axillary and internal mammary positive nodes have a very poor prognosis (10-year survival 37.3%) while patients with either axillary metastases only or internal mammary metastases only have an intermediate less grave prognosis (59.6% and 62.4%, respectively). As regards the risk of internal mammary nodes involvement, it appears that knowing the age, the size, and the axillary nodes status, it is possible to calculate with good approximation the probability of their invasion.

Stage I melanoma of the skin: Evaluation of prognosis according to histologic characteristics

The prognosis for Stage I melanoma of the skin was evaluated on the basis of histologic characteristics of 699 primary tumors collected by the W.H.O. Melanoma Group from September 1967 to September 1975. Variables considered were maximum tumor thickness, levels of invasion, histologic type, number of mitoses, cell type, growth pattern, inflammatory reaction, angioinvasion, ulceration. When considered as single factors, these criteria, but cell type and inflammatory reaction, significantly affected survival (P < 0.05). However, when each criterion was adjusted by maximum tumor thickness, the number of mitoses and ulceration only were found to be still significant. The type of cells, which is not significant by itself (P = 0.92), becomes significant (P = 0.02) when adjusted by maximum thickness. The most important prognostic factor was maximum tumor thickness (P = 10−9). Using this criterion this series was divided into three groups: (1) “good prognosis” with maximum thickness not exceeding 2 mm and a five‐year survival rate of over 80%; (2) “intermediate prognosis” with maximum thickness between 2.01–4.00 mm and a five‐year survival rate between 50 and 80%; (3) “poor prognosis” with maximum thickness greater than 4.01 mm and five‐year survival rate of under 50%. All other prognostic criteria were evaluated within each group and it was found that the “intermediate prognosis” group cannot be divided into subgroups with different survival. The best survival was observed in patients with primary tumor not thicker than 2.00 mm with no ulceration (P = 0.01) or with spindle cells (P = 0.03); the worse survival was observed in patients with primary melanoma thicker than 4 with ulceration (P = 0.04) or with more than one mitosis per high power field (P = 0.04).

Prognosis of breast cancer with axillary node metastases after surgical treatment only.

Out of 753 patients with breast cancer treated with radical mastectomy from 1968 to 1970 at the National Cancer Institute of Milan, Italy, 308 had histologically proven positive nodes. The number of positive nodes was not dependent on the location of the primary tumour, its diameter and the patients age. Extracapsular invasion was related to the number of positive nodes at a statistically significant level: P value 2 X 10(-9). Survival was influenced by the number of positive nodes and extension of metastases beyond their capsule and age. Each of these criteria had an independent impact on survival. Three subgroups with different prognosis were identified in patients older than 40: (a) with a single involved node and 69.9% 10 year survival rate, (b) patients with two or more nodes with metastatic deposit still confined within node capsule and 47.4% 10 year survival rate, (c) patients with two or more involved nodes and extracapsular invasion and 25.3% 10 year survival rate. In patients younger than 40 no subgroup was identified: this group had an intermediate 10 year survival rate (50.9%). The authors conclude that there is a need (a) of re-consideration of the prognosis of patients with positive nodes and (b) to agree on the definition of high-risk patients.

Evaluation of the risk of multiple primaries in malignant cutaneous melanoma

The evaluation of the risk of a second primary melanoma has been done on a series of 521 cases of malignant melanoma observed at the National Cancer Institute of Milan from September 1967 to December 1974. It has been found that a malignant melanoma patient is about 900 times more likely to have a second primary than an individual in the general population is likely to contract the disease. The risk is age and sex dependent.

BANS. A cutaneous region with no prognostic significance in patients with melanoma.

Data of 769 Stage I melanoma patients treated from 1967 to 1974 by the W.H.O. Melanoma Group centers were analyzed. The mean follow‐up period was 10.3 years. Of the 769 patients (239 males, 530 females), 133 had a primary in the BANS region. The observed ten‐year actuarial survival was 54.8% for the 133 BANS patients and 54.9% for the remaining 636. Multivariate analysis showed that thickness was the most important prognostic factor (P = 10−9); ulceration and sex were also found to be significantly related to survival (P values were 5 × 10−4 and 10−5, respectively). The other criteria were no longer significant when adjusted by these three. In particular, the BANS region had a P value of 0.6. To evaluate the effect of BANS in thin melanoma, a subgroup of 152 patients (29 BANS, 123 other) with primary thickness between 0.76 and 1.69 mm was studied. Multivariate analysis showed that no criteria are significantly associated with prognosis of these patients. Observed actuarial survival rate for BANS patients was 69.2% and for the remaining 123, 66.7%. The number of deaths was 8/29 and 27/123. The BANS region does not appear to be of importance in the prognosis of Stage I melanoma patients.

Early local complications following colostomy closure in cancer patients

Early surgical complications following colostomy closure in 65 cancer patients operated on at the Istituto Nazionale Tumori of Milan were evaluated retrospectively. The overall complication rate was 24.6 per cent, including infections (13.8 per cent), fistulas (6.1 per cent), wound dehiscence (3.0 per cent), and distal stenosis (1.5 per cent). Type and rate of complications were analyzed to find a correlation with type, site, and location of colostomy, technique of closure, presence or absence of drains, or time interval between construction and closure of colostomy. No statistically significant association between the aforementioned factors and occurrence and rate of complications was found. The authors think, therefore, that surgical attention, including meticulous manipulation of the stoma, avoidance of contamination of the wound, tension of sutures, dead spaces, and collection of blood in the wound, and use of antibiotics and antiseptics are the most important principles to minimize postoperative complications.

Metastatic Spread of Stage I Melanoma of the Skin

1164 patients with stage I melanoma of the skin who were submitted to wide excision only of the primary tumor were studied to evaluate the rates of regional lymph node and distant metastases. Of these, 516 (44.3%) had a recurrence of the disease which was at regional lymph nodes in 264 (22.7%), at distant sites in 91 (7.8%), and simultaneously at regional lymph nodes and distant sites in 161 (13.8%). Most of the patients had a relapse within 5 years: regional node metastases were most frequently observed during the first 3 years, and distant metastases appeared later. The ratio regional:distant metastases was not different (P > 0.05) when subgroups of patients were considered according to prognostic criteria (sex, site of origin, levels, thickness, ulceration). Sex, levels, thickness and ulceration were found to be significantly related with the frequency of recurrences (regional and distant). It is concluded that the prognostic criteria considered do not predict whether the tumor will metastasize to regional nodes or to distant sites.

Combined Effect of Transfusion and Blood Groups on the Survival of Patients With Breast Cancer. A Clinical Study of 901 Patients

Previous reports by the authors and by others have shown that trans fusion adversely affects the survival of cancer patients. To delineate fur ther the mechanism of action of blood transfusion on biological behavior of cancer, the authors studied the role of the major blood groups ABO in 901 patients who had all undergone radi cal surgery for operable primary breast cancer and among whom 294 had received at least one unit of whole blood perioperatively. Multivariate analysis using Coxs regression models on life tables was used. It was found that the adverse effect of transfusion on survival was a blood group-related phenomenon manifesting its action in patients with blood groups A and B (P = 0.0006 and P = 0.006 respectively). The most im pressive effect of transfusion was seen in patients whose age was be tween forty-one and fifty (51.9% ten- year actuarial survival in 47 transfused patients compared with 73.9% in 70 nontransfused ones). A hypothesis is presented suggest ing that transfusion exerts its effect on the hemostatic system, promoting clotting in group A and B patients and fibrinolysis in group O and AB patients, and thus affects metastatic cascade, with results that have been presented in this series.

Breast Cancer: Primary Tumor Characteristics Related to Lymph Node Involvement

From November 1st 1977 to August 31st 1978, 842 consecutive patients with operable breast cancer were observed at the National Cancer Institute of Milan. Characteristics of the primary tumor and the status of regional lymph nodes were evaluated at clinical and postsurgical examination: it was found that qualitative characteristics of the primary were properly defined by clinicians, who usually overestimated maximum diameter of the primary. The status of regional lymph nodes is not reliable at clinical examination: 34.5 % of clinically uninvolved nodes were found to contain metastatic growth at histologic examination. Age of patients, maximum diameter of the primary, histologic type and quadrant of origin of the primary tumor were significantly related to the frequency of regional node metastases. Multifactorial analysis showed that the last three factors were independent variables, while age, which is significant by itself, loses importance when adjusted by at least one of the other three factors. Frequency of extension of node metastases beyond the lymph node capsule was found to be related to the number of involved nodes: maximum diameter, histologic type and site of origin are significantly related to the frequency of extracapsular invasion. This study confirms that the evaluation of the status of regional lymph nodes is not reliable at clinical examination and indicates that characteristics of the primary may be useful in predicting regional lymph node involvement. The direct correlation between the number of involved nodes and the frequency of infiltration beyond the capsule suggests that prognosis of patients with positive nodes depends more on this factor than on the number of involved nodes.