Rosen's Breast Pathology, 4e

897

Unusual Clinical Presentation of Carcinoma

be reduced in breast carcinomas that arise in elderly women. 71 Others have reported that the presence of ALN metastases in breast carcinoma patients 34 years or younger is significantly related to p53 positivity and high proliferative index. 72 Walker et al. 73 found an inverse relationship between p53 immunopositivity and age, with positive staining in 67% and 37% of tumors from women 25 to 29 and 50 to 67 years of age, respectively. Proliferative rate, assessed by Ki67 immu­ nostaining, was also inversely related to age, with 72% of tu­ mors in patients 25 to 29 classified as “high” compared with 40% in the group 50 to 67 years of age. The proportion of ER-positive invasive carcinomas is higher in postmenopausal than in premenopausal women, and there is evidence indicating that the growth rate and positive ER status of breast carcinomas are inversely re­ lated. 71 Although breast carcinomas in younger women are now more often detected before involving lymph nodes than 10 years ago, a larger percentage is triple-negative. 74 The proportion of ER- and PR-positive tumors does not in­ crease significantly with advancing age in postmenopausal women 65 years or older. 75 Gennari et al. 76 reported that the frequency of estrogen and progesterone positivity was sig­ nificantly higher in postmenopausal women 65 years of age or older when compared with postmenopausal women 50 to 64 years old. The older postmenopausal women had a sig­ nificantly lower frequency of HER2-positive tumors. These observations appear to support the perception that breast carcinoma tends to have less aggressive biologic features and a more favorable clinical course in the elderly. Nonetheless, no significant differences in prognosis were observed when patients younger than 35 and older than 75 were matched on the basis of tumor stage. 66 Breast Conservation Therapy Women 40 years of age or younger are more likely than older patients to develop breast recurrences after breast- conserving surgery and radiotherapy for invasive carci­ noma. 77–81 This phenomenon has been attributed to more frequent poorly differentiated carcinomas in this age group, difficulty in determining extent of carcinoma intraopera­ tively, and a high prevalence of carcinomas with an extensive intraductal component or lymphatic emboli in peritumoral tissue. 78 The addition of adjuvant chemotherapy appears to lower the risk of breast recurrence in women younger than 35 years who are treated by breast conservation. 79,82,83 Chest wall irradiation has been recommended if carcinoma is present at or close to (less than 5 mm) the deep margin of a mastectomy. 84 The risk of breast recurrence after breast con­ servation does not appear to be affected by a family history of breast cancer. 85 Vicini et al. 86 reported that patients younger than 45 years of age had a significantly greater risk of breast recurrence after conservation therapy (excision and radiotherapy) for intraductal carcinoma than women who were 45 years or older. The frequency of invasive recurrence was substan­ tially greater in the younger age group. When the volume of tissue was considered in the analysis, age at diagnosis

proved not to be significantly related to recurrence risk, and it was concluded that the higher local failure rate in patients younger than 45 was related to smaller excision volumes in this age group. Arvold et al. 87 studied 1,434 consecutive patients with in­ vasive breast cancer who received breast conservation ther­ apy over a 10-year period ending 2006. Ninety-one percent received adjuvant systemic therapy. The median follow-up was 85 months, and the overall 5-year cumulative incidence of local recurrence was 2.1%. The 5-year cumulative inci­ dence of local recurrence was 5.0% for ages 23 to 46 years; 2.2% for ages 47 to 54 years; 0.9% for ages 55 to 63 years; and 0.6% for ages 64 to 88 years. On multivariable analysis, increasing age was associated with decreased risk of local recurrence. Carcinoma in Elderly Women The Cancer and Leukemia Group B (CALGB) trial 9343 ex­ amined the contribution of radiation after lumpectomy in women aged 70 and older with ER-positive node-negative breast carcinomas that were 2 cm or smaller. 88 After tumor excision, the patients were randomized to tamoxifen alone versus radiation plus tamoxifen. An update of this study with a 10.5-year median follow-up showed that 98% of the radiation plus tamoxifen group and 92% of the tamoxifen- only group were recurrence free. 89 Based on the 6% lower frequency of ipsilateral breast tumor recurrence for the ra­ diation group, it was estimated that 300 women would have to be radiated to prevent 20 local recurrences. The fact that the two groups did not differ significantly in overall 10-year survival and breast-cancer–specific survival suggests that the small difference in the frequency of breast recurrence did not significantly affect survival 10 years after initial treatment. Results of the ongoing Postoperative Radiation in Minimal Risk Elderly Patients (PRIME II) trial 90 in the United Kingdom may further define the effect of omis­ sion of radiation in elderly patients with hormone recep­ tor node-negative invasive carcinomas. Until then, the advantages of radiation after breast conservation ther­ apy in this subset of elderly patients should be weighed against its morbidities, and the decision to radiate should be individualized. Genetic Considerations Some special considerations are to be kept in mind regard­ ing genetic abnormalities and breast carcinoma in young adult women. “Secretory carcinoma” is the most common malignant epithelial neoplasm encountered in children. Its occurrence in younger patients accounts for the previously used term juvenile carcinoma, but it can be found in adult women of all ages. Because secretory carcinoma almost always has a bal­ anced chromosomal translocation, t(12:15)(p13;q25) that leads to fusion of the ETV6 and NTRK3 genes, 91 it has been referred to as “a genetically defined carcinoma entity.” 92