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Early Breast Cancer

Chapter 12 - Breast Cancer in the Senior Patient

Surgery

The surgical approach in older patients with breast cancer should not differ from that in younger women. Depending on the clinical situation, breast conserving surgery (BCS) or mastectomy combined with sentinel node biopsy or axillary dissection are suitable options. Two randomised trials, conducted in patients with clinically node-negative, hormone receptor–positive (HR+), early breast cancer who received tamoxifen, have shown that the omission of axillary clearance did not affect breast cancer specific survival and disease free survival (DFS), and was associated with a very low local relapse rate. This approach remains exploratory and should be reserved for patients who present with contraindications to or refuse sentinel node biopsy.

Primary Endocrine Therapy

Primary endocrine therapy alone has been shown to be inferior to surgery in fit women, and should only be offered to elderly individuals with HR+ tumours who have short estimated life expectancy (<2–3 years), who are considered unfit for surgery despite optimisation of medical conditions, or those who refused surgery.

Radiotherapy

Post-mastectomy chest wall radiation should be considered in selected elderly women with a high risk for relapse, i.e. ≥4 positive nodes or large tumours (pT3/T4). The cost-benefit ratio of post-mastectomy radiotherapy should be discussed in patients with limited life expectancy (<5 years).

For early invasive breast cancer, postoperative whole breast radiotherapy (WBRT) is considered the standard of care for fit patients following BCS. WBRT was associated with an 8% absolute improvement in the 10-year locoregional recurrence (CALGB 9343). However, omission of WBRT in patients with HR+ early stage breast cancer who received tamoxifen, caused no disadvantage in terms of overall survival (OS), distant DFS, or breast preservation. Based on these findings, adjuvant endocrine treatment alone may be a reasonable therapeutic option for some women after BCS. Hypofractionated radiation schedules have similar locoregional control and DFS benefits as standard WBRT. Accelerated partial breast radiotherapy with multicatheter brachytherapy in patients with low risk [pT1-2a (T≤3cm), pN0/pNmi,M0] early breast cancer is not inferior to adjuvant WBRT with respect to 5-year local control, DFS, and OS. European and US guidelines indicate that patients with good prognosis can be treated with perioperative radiation only to the tumour bed.

Adjuvant Endocrine Treatment

Endocrine therapy is the standard of treatment for elderly patients with HR+ tumours. The benefits of tamoxifen and aromatase inhibitors (AIs) are age-independent, although the efficacy is slightly greater with aromatase inhibitors. However, elderly patients are more vulnerable to toxicities, and competing comorbidities must be considered when planning the treatment strategy. AIs are generally preferred to tamoxifen because of the lower risk for thrombosis and endometrial cancer. Bone loss, a typical side effect of AIs, is a critical issue in elderly patients, since pre-existing decrease in bone mineral density and osteoporosis are prevalent. Although, appropriate use of bone-modifying agents may be a solution (with possible survival benefit as indicated by the bisphosphonate meta-analysis).

Initial treatment should either be with tamoxifen or an AI. It is recommended to consider patients started on tamoxifen to switch to an AI after 2–3 years. The extended approach, defined as administration of AI after five years of treatment with tamoxifen, is associated with a significant DFS advantage, but only in patients younger than 60 years (trial MA.17). Nevertheless, the study showed no interaction between treatment and age, indicating a probable similar effect of the AI among all age groups. Omission of endocrine therapy may be an option for patients who have a tumour with a very low risk (pT1aN0) for recurrence or have life-threatening comorbidities.

Adjuvant Chemotherapy

The benefit of adjuvant chemotherapy is often perceived to progressively decrease with increasing age. However, patients aged 70 years and older achieve similar advantage as those aged 50 to 70 years. Patients with hormone receptor–negative (HR-) tumours gain significantly more from chemotherapy than HR+ tumours.

Two retrospective studies, based on the Surveillance, Epidemiology, and End Results (SEER) database, have shown an OS advantage from adjuvant chemotherapy in elderly patients with oestrogen-receptor negative tumours. The benefit was observed only in patients with node-positive tumours in one of the two studies.

Polychemotherapy, doxorubin and cyclophosphamide (AC) x 4 cycles or classical cyclophosphamide, methotrexate, and fluorouracil (CMF) x 6 cycles, is superior to single-agent adjuvant chemotherapy (capecitabine). Four cycles of an anthracycline-containing regimen are usually preferred over CMF. Taxanes are associated with increased toxicity in older patients compared with younger women, but can be added to anthracyclines in high-risk healthy elderly patients, or replace anthracyclines to reduce the cardiac risk. Adjuvant docetaxel and cyclophosphamide (TC) is superior to AC even in older patients (≥65 years). TC-related febrile neutropaenia has been reported in 8% of elderly patients in a clinical trial. However, higher rates have been reported in actual clinical practice, supporting the use of primary prophylaxis with granulocyte colony stimulating factor (G-CSF), as indicated by the guidelines.

Tumour biology, risk of relapse, and patient’s life expectancy, rather than age, must influence clinical decision-making and determine the appropriateness of adjuvant chemotherapy for an elderly woman with breast cancer. Healthy older patients with node-positive, HR- tumours derive the largest benefit from adjuvant chemotherapy. There is no evidence that unfit patients will benefit from adjuvant chemotherapy, as the dose-intensity needed cannot be maintained. Paclitaxel monotherapy failed to show non-inferiority over combination AC in a randomised phase III study (CALGB 40101). However, paclitaxel was better tolerated, and the estimated absolute difference for OS was only 1%. These features might justify the use of single agent paclitaxel in high-risk patients who are unfit for standard polychemotherapy.

Trastuzumab

Although only a few patients aged ≥70 years have been included in trials evaluating the role of trastuzumab in the adjuvant setting, it is recommended that all fit HER2-positive elderly breast cancer patients without contraindications (i.e. cardiac disease) should be offered trastuzumab in combination with chemotherapy. The cytotoxic partners should preferably be anthracycline-free to diminish the risk of cardiotoxicity associated with trastuzumab. A cost-benefit ratio evaluation is needed for elderly women with low risk HER2 small tumours (i.e. T<1cm). Currently, no clinical data is available to support treatment with trastuzumab alone. However, in certain situations when chemotherapy is not suitable, giving trastuzumab monotherapy may be justifiable.

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