Rosen's Breast Pathology, 4e

896

Chapter 33

with mastectomy. The disease-free interval was shorter in patients with hormone receptor–positive carcinoma after a median follow-up of 78 months. The overall 5-year survival was 80%, suggesting that the prognosis of patients in this age group is improved by earlier diagnosis and the use of mod­ ern treatment modalities in addition to surgery. Patients 40 to 49 Years of Age Most studies of clinical issues in the diagnosis of breast ­carcinoma in younger women have focused on the ­relatively large group of patients 40 to 49 years of age. A report of 809 consecutive patients biopsied for nonpalpable, mam­ mographically detected lesions revealed carcinoma in 5% of ­biopsies prior to age 40, in 15% of biopsies in the 40- to 49-year age group, and in 34% of biopsies from women older than 50 years. 61 Twenty-five percent of carcinomas in women 40 to 49 years old and 16% in women 50 years or older were noninvasive. Mean tumor size was the same in both groups (1.5 cm), but nodal metastases were present more often in the 40- to 49-year age group (25%) than in the group 50 years or older (17%). McPherson et al. 62 investigated the relationship of method of tumor detection to prognosis in women 40 to 49 years of age using a database of patients diagnosed in North Dakota, South Dakota, and Minnesota. When compared with the risk of dying from carcinomas detected by mammography, the RRs of dying from carcinomas detected by breast self- examination (BSE) (2.5), clinical breast exam (CE) (2.7), or discovered by the patient incidentally (2.8) were signifi­ cantly greater. The mean size of mammographically detected ­tumors (1.9 cm) was significantly smaller than those in the CE (2.3 cm), BSE (2.8 cm), and incidental (2.9 cm) groups. After adjusting for stage (tumor size and nodal status), the RRs of dying of carcinomas were greater when detected by BSE (1.5), CE (1.9), or incidentally (1.6), when compared with tumors detected by mammography. These results sug­ gest that mammography makes a contribution to improv­ ing the prognosis of women with carcinoma 40 to 49 years of age. The implications of these observations for mammo­ graphic screening in this age group and in women younger than 40 years remain controversial. Clinical problems encountered in the diagnosis of breast carcinoma in women 49 years and younger were detailed in a report by Lannin et al. 63 The authors analyzed the re­ sults of mammography and physical examination in a con­ secutive series of patients evaluated in a university hospital clinic in order to compare women 20 to 49 years of age with those 50 years or older. The positive predictive value (PPV) of mammography was 28% for women younger than 50 and 53% in those 50 years or older. The PPV of an abnor­ mal physical examination resulting in biopsy was 11% and 57% in women younger than 50 years and 50 or older, re­ spectively. There was also a statistically significant differ­ ence in the sensitivity of mammography between patients younger than and 50 years or older (68% and 91%, respec­ tively). The sensitivity of physical examination did not dif­ fer significantly between the two groups. This discrepancy

was not observed between nonpalpable and palpable tumors in women younger than 50 years (mean tumor size, 4.0 and 3.4 cm, respectively). These results led the authors to con­ clude that physical examination and mammography were less sensitive in women 20 to 49 years old when compared with women 50 years or older. They suggested that “tumors in young women are nonpalpable, not because they are small, but because of background density of the mammary tissue or because of the more diffuse growth pattern of tumors at this age. These are exactly the same reasons mammography is less sensitive in young women.” The addition of FNA or needle core biopsy for abnormalities detected by mammog­ raphy and clinical examination constitutes the “triple test” for the diagnosis of breast tumors, a method that improves diagnostic accuracy, especially in younger women. 64 Pathology Most pathologic features of breast carcinoma do not differ appreciably in adults who are relatively young or old. 65–68 Tu­ mor size is not significantly different when young and elderly patients are compared. 67 Approximately 50% of patients have tumors 2 cm or smaller, 40% have tumors in the 2.1- to 5.0-cm range, and the rest have tumors larger than 5 cm. The left breast is more often affected than the right in both age extremes. The location of the tumor (lateral vs. medial-central), the overall frequency of bilaterality, and concurrent bilaterality are not significantly different at the extremes of the age distribution. Several differences with respect to tumor type exist at the extremes of age. 66 Patients younger than 35 have a higher proportion of medullary carcinoma, and lower proportions of infiltrating lobular (2.0% vs. 11.0%) and of mucinous car­ cinoma (1.0% vs. 7.0%), in comparison with patients older than 75. A marked lymphocytic reaction occurs in a higher proportion of women younger than 35 than in the elderly group (34% vs. 12%). Collins et al. 69 analyzed clinical and pathologic data for 657 patients with intraductal carcinoma (ductal carcinoma in situ [DCIS]) to identify features that might explain the greater risk for local recurrence in young women after breast- conserving therapy. Four age groups were compared, with the youngest consisting of 111 women less than 45 years of age at diagnosis, who proved to have significantly more ex­ tensive DCIS and more frequent lobular cancerization than women older than 45. DCIS was detected by mammography significantly less often in women younger than 45 years than in any of the older cohorts. There was no statistically signifi­ cant relationship between age and the following features of DCIS: architectural type, nuclear grade, comedonecrosis, or the expression of receptors for ER, PR, or epidermal growth factor receptor 2 (EGFR2).

Prognostic and Predictive Markers in Invasive Carcinoma

Studies of growth rate and tumor cell kinetics suggest an inverse relationship between patient age at diagnosis and the prolifera­ tive activity in the invasive carcinoma. 70,71 Growth rate tends to