Individualized Care for Older Patients With Localized Breast Cancer
Individualized Care for Older Patients With Localized Breast Cancer
Breast cancer is a heterogeneous disease composed of four main subtypes of breast carcinomas: luminal type A, luminal type B, HER-2-positive and basal-like, as is based on genetic profiling. The data on frequency of molecular subtypes of breast cancer in older women defined by gene expression is limited. Jenkins et al. showed that among 293 patients 70 years of age or older, the basal-like tumors represented 13%, HER-2 positive 13%, luminal type A 35% and luminal type B 28% of breast cancers analyzed by PAM50 gene set. A retrospective Belgian study that examined the influence of age on the incidence of luminal subtypes of breast cancer showed that even though women older than 70 years develop mostly the less aggressive luminal type A breast cancer, 19 and 26% of women older than 70 and 80 years, respectively, developed luminal type B tumors that are associated with a high proliferation rate, high grade, large size and nodal invasion.
Two large epidemiologic studies using the San Antonio breast cancer database and the SEER registry explored the clinical and biological characteristics of elderly women with breast cancer in the USA. Both studies showed statistically significant differences in histology based on age, with older patients having more lobular and mucinous carcinomas. In the San Antonio breast cancer database, patients aged 85 years or older had larger tumors at diagnosis than younger patients. This finding may reflect reluctance of older patients to seek medical advice or indicate that fewer older patients undergo screening mammography. Despite the larger tumor size, older patients had tumors with more favorable biological characteristics. The percentage of ER-positive breast cancers increased with age from 83% in women aged 55–64 years to 87, 90 and 91% in women aged 65–74, 75–84 and 85 years or older, respectively. Compared with younger patients, older patients had more tumors that had a low S-phase fraction and normal p53, and were negative for EGFR and HER-2. The data from SEER showed similar findings with increased ER-positive breast cancer with increasing age.
Very limited data exist on basal type of breast cancer in older women. In general, the basal-like subtype characterized by lack of ER, progesterone receptor (PR) and HER-2 non-overexpression (called triple negative) is associated with younger age, African–American race, aggressive histology, poor prognosis, shorter survival and BRCA1-related breast cancer. The population-based California Cancer Registry data from 1999–2003 showed that in women diagnosed with invasive breast cancer for whom tumor markers were known, the majority (63%) of triple negative breast cancers were diagnosed in women younger than 60 years, still, almost 20% of triple negative breast cancers occurred in women 70 years or older. One single institution retrospective study comparing tumor characteristics and recurrence patterns of triple negative breast cancer between women younger than 65 years and those aged 65 or older showed that mean tumor size, tumor grade and number of positive lymph nodes did not differ significantly between both age groups. TNBC patients aged <65 years experienced significantly more local recurrences, bone metastases and secondary lymph node metastases compared to older TNBC patients. There was no significant difference in the occurrence of distant visceral metastases. Older women with TNBC received significantly less chemotherapy than younger patients. Few retrospective studies comparing the prognosis of younger and older women with TNBC suggest that older patients may have a better or at least equivalent outcome despite not having received adjuvant chemotherapy.
The analysis of 12 population-based SEER registries estimated the prevalence of HER-2-positive early stage breast cancers at 19% of women aged 49 years or younger and 15% of women aged 50 years or older. The population-based Netherlands Cancer Registry study showed that the percentage of HER-2-positive tumors decreased with increasing age from 22% in women younger than 40 years to 10% in women age 70 years or older. To our knowledge, there are no data on outcome of older women with HER-2-positive breast cancer.
In summary, there is a need for more studies to specifically look at the long-term clinical outcomes of specific subtypes of breast cancer in older women in order to know whether the biology of given subtype varies between younger and older women.
Cancer Biology
Breast cancer is a heterogeneous disease composed of four main subtypes of breast carcinomas: luminal type A, luminal type B, HER-2-positive and basal-like, as is based on genetic profiling. The data on frequency of molecular subtypes of breast cancer in older women defined by gene expression is limited. Jenkins et al. showed that among 293 patients 70 years of age or older, the basal-like tumors represented 13%, HER-2 positive 13%, luminal type A 35% and luminal type B 28% of breast cancers analyzed by PAM50 gene set. A retrospective Belgian study that examined the influence of age on the incidence of luminal subtypes of breast cancer showed that even though women older than 70 years develop mostly the less aggressive luminal type A breast cancer, 19 and 26% of women older than 70 and 80 years, respectively, developed luminal type B tumors that are associated with a high proliferation rate, high grade, large size and nodal invasion.
Two large epidemiologic studies using the San Antonio breast cancer database and the SEER registry explored the clinical and biological characteristics of elderly women with breast cancer in the USA. Both studies showed statistically significant differences in histology based on age, with older patients having more lobular and mucinous carcinomas. In the San Antonio breast cancer database, patients aged 85 years or older had larger tumors at diagnosis than younger patients. This finding may reflect reluctance of older patients to seek medical advice or indicate that fewer older patients undergo screening mammography. Despite the larger tumor size, older patients had tumors with more favorable biological characteristics. The percentage of ER-positive breast cancers increased with age from 83% in women aged 55–64 years to 87, 90 and 91% in women aged 65–74, 75–84 and 85 years or older, respectively. Compared with younger patients, older patients had more tumors that had a low S-phase fraction and normal p53, and were negative for EGFR and HER-2. The data from SEER showed similar findings with increased ER-positive breast cancer with increasing age.
Very limited data exist on basal type of breast cancer in older women. In general, the basal-like subtype characterized by lack of ER, progesterone receptor (PR) and HER-2 non-overexpression (called triple negative) is associated with younger age, African–American race, aggressive histology, poor prognosis, shorter survival and BRCA1-related breast cancer. The population-based California Cancer Registry data from 1999–2003 showed that in women diagnosed with invasive breast cancer for whom tumor markers were known, the majority (63%) of triple negative breast cancers were diagnosed in women younger than 60 years, still, almost 20% of triple negative breast cancers occurred in women 70 years or older. One single institution retrospective study comparing tumor characteristics and recurrence patterns of triple negative breast cancer between women younger than 65 years and those aged 65 or older showed that mean tumor size, tumor grade and number of positive lymph nodes did not differ significantly between both age groups. TNBC patients aged <65 years experienced significantly more local recurrences, bone metastases and secondary lymph node metastases compared to older TNBC patients. There was no significant difference in the occurrence of distant visceral metastases. Older women with TNBC received significantly less chemotherapy than younger patients. Few retrospective studies comparing the prognosis of younger and older women with TNBC suggest that older patients may have a better or at least equivalent outcome despite not having received adjuvant chemotherapy.
The analysis of 12 population-based SEER registries estimated the prevalence of HER-2-positive early stage breast cancers at 19% of women aged 49 years or younger and 15% of women aged 50 years or older. The population-based Netherlands Cancer Registry study showed that the percentage of HER-2-positive tumors decreased with increasing age from 22% in women younger than 40 years to 10% in women age 70 years or older. To our knowledge, there are no data on outcome of older women with HER-2-positive breast cancer.
In summary, there is a need for more studies to specifically look at the long-term clinical outcomes of specific subtypes of breast cancer in older women in order to know whether the biology of given subtype varies between younger and older women.
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