8. Breast cancer in elderly patients – Breast Cancer

 

Background 8.2

Numerous articles show that various parameters of geriatric assessment are related to outcome. Interventional evidence is also increasing in this area: Only recently, a large study on the adaptation of therapy in frail patients showed a significant improvement in functionality and reduction in mortality by means of a geriatric frailty assessment prior to surgery, although no breast cancer patients were included.

In a non-randomised study it was also shown that in the intervention group with a CGA (comprehensive geriatric assessment) fewer therapy modifications were necessary and the planned therapy could be completed with fewer toxicities. Overall survival in this group has not yet been investigated [1571], [1572], [1573], [1574].

 

 

Background 8.3

Increasingly, geriatric assessment parameters are used in observational studies and in randomized studies, which are subsequently available for (mostly secondary) analyses. For example, the ELDA study showed that the number of comorbidities and activities of daily living (ATL) (in addition to age and therapy with docetaxel) was associated with severe non-hematological toxicities [1579].

Hamaker was also able to show that the number of geriatric syndromes from a complete geriatric assessment was associated with the occurrence of grade 3-4 toxicities. In contrast, the results of the Groningen Frailty Indicator showed no association with the occurrence of grade 3-4 toxicities in this cohort. Polymedication was the best predictor of Grade 3-4 toxicity after chemotherapy [1580].

Hurria has associated different geriatric and non-geriatric parameters with toxicity in different studies in patients with different neoplasms, as well as Cough-Gorr et al. These include falls, mobility, hearing, creatinine clearance, comorbidities, cognition, social status. CGA, especially cognition and functionality, was also associated with 7-year survival [1575], [1581].

 

 

Background 8.4 to 8.6

The indications for breast-conserving surgery or mastectomy are basically no different for older patients than for younger patients. However, co-morbidities such as cardiac diseases should be taken into account, which may make follow-up radiation of the mamma impossible and thus also influence the decision on the type of surgery. SNB (sentinel node biopsy) is also the therapy of choice for older patients with clinically negative axilla. Even in affected SLN, the ACOSOG-Z0011 study was able to show that under certain conditions (BET, T1/2 and 1-2 positive sentinels, systemic therapy) axillary lymphonodectomy can be dispensed with, without negative influence on locoregional and systemic control. In the case of a primarily clinically positive axilla, axilla dissection is indicated as in the younger patient. The renunciation of axilla staging can be considered in individual cases depending on age and comorbidities.

Based on the Cochrane review by Morgan et al. (2014) of 7 studies in women aged 70 and older with endocrine positive breast cancer, no benefit was found for surgery or primary endocrine therapy with tamoxifen in terms of breast cancer mortality (HR 0.98, 95% CI 0.81 to 1.20, P = 0.8, follow-up up to 12 years, low heterogeneity). An improved local control was observed in operated patients [1582].

 

 

Background 8.7

At a very favourable stage and with a favourable biology, e.g. pT1 pN0 ER and PgR positive, G1-G2 has a low benefit of endocrine therapy due to the low risk of recurrence. In a Danish cohort study, the absence of endocrine therapy in patients aged 60-74 years showed no difference in survival compared to the normal population for pT1a,1b pN0 tumors G1 ductal or G1 or 2 with lobular histology.

 

 

Background 8.8

There are numerous age-associated factors that can influence the pharmacokinetics of chemotherapeutic agents. These include absorption through reduced gastric secretion and motility. The distribution volume of fluids may change due to increased body fat content, decreased intracellular water and reduced albumin concentrations. Metabolism in the elderly is also altered by reduced liver flow, reduced liver size and also changes in the microsomal P-450 system. Pharmacodynamically important with increasing age is the reduced glomerular filtration rate and thus impaired renal function.

 

 

Background 8.9

The most recent and largest study on this subject at least suggests this, especially for docetaxel [533], even though the meta-analysis (without this new study from 2015) had not yet found any evidence for this [1584].

 

 

Background 8.10

In most chemotherapy studies, older women were either not included or were underrepresented. The available data are therefore often only derived from subgroup analyses of older patients who were not included in these studies. Based on the available evidence and according to the SIOG task force, anthracycline taxane containing sequence regimens, e.g. 4 x EC followed by 12 x paclitaxel weekly, 4 x docetaxel/cyclophosphamide and 4 x epirubicin/cyclophosphamide, are recommended regimens. The CMF regimen may also be an option in individual cases, was superior to capecitabine monotherapy in a randomized trial and was as effective as docetaxel weekly, but with significantly fewer non-hematological side effects and better quality of life. For taxanes, weekly paclitaxel doses are preferable to (weekly) docetaxel. Primary prophylaxis with growth factors should be considered in older patients. The intensity of the therapy should depend on the tumour stage, the tumour biology and the general condition of the patient.

The increased risk of cardiotoxicity should also be considered in older patients with anthracycline therapy. In a retrospective study of 630 patients with doxorubicin-based therapy, age was a risk factor for cardiac side effects, independent of performance status and comorbidities. In a further retrospective study of 40 000 66-80 year old women in the SEER database who received adjuvant chemotherapy, a steadily increasing rate of cardiac impairment of varying degrees was found up to 10 years after completion of adjuvant therapy.

Older patients under therapy with anthracyclines also have a higher risk of developing MDS or AML than younger patients. In a recent study by Freedman, however, the absolute risk remained low with about 1% of patients treated in patients between 65 and 70 years of age (<65% 0.4%). The hazard ratio (HR) of = 5 (with large Cl) for anthracycline was, however, the strongest predictive factor for developing AML/MDS syndrome.

 

 

Background 8.11

633 women with early breast cancer stage I-III and older than 65 years (65% ≥70 years) were randomized to 6 x CMF / 4 x AC (depending on the investigator's preference) or 6 cycles of Capecitabine. In hormone receptor-positive disease, endocrine therapy was started after the end of chemotherapy. Disease-free and overall survival was significantly higher in the CMF/AC group (85% vs 68% and 91% vs 86%) compared to the capecitabine group.

 

 

Background 8.12

The proportion of HER2-positive breast cancer patients is not exactly known. However, on the basis of retrospective studies it can be assumed that it is similarly high in older women as in younger women (10% to 20%) [1592].

The tumor biological behavior does not differ from that in younger women.

Since the drug treatment of breast carcinoma should be based on tumor biological factors, there is no reason to deviate from the therapy recommendations for younger women [1578], [1593].

However, age-related changes (higher proportion of cardiac comorbidities, reduction of the bone marrow reserve) must be included in the therapy concept.

Anthracycline-free chemotherapy regimens in combination with trastuzumab showed an identical efficacy on [1595]. In a randomized phase III study, the combination of docetaxel-cyclophosphamide with doxorubicin-cyclophosphamide was superior to [1594]. Due to the expected myelotoxicity, granulocyte stimulating factors (GCSF) should be used prophylactically according to the ESMO guidelines.

 

 

Background 8.13

The Pase-II study of CALBG by Tolaney et al. showed excellent 3-year survival (98% survival rate) for hormone receptor-positive, HER2-positive, nodal-negative tumors.

In this study, patients were treated for 12 weeks with weekly paclitaxel therapy in combination with trastuzumab. After 12 weeks, treatment with trastuzumab was continued for a total of 1 year and endocrine therapy was started. In this study one third of the women were older than 60 years. Due to the reduced toxicity of this combination, it appears to be particularly suitable as an adjuvant treatment option for patients with cardiac comorbidities [1596] and HER2-positive breast cancer.