More on Facing the Reality of Our Aging Population With Breast Cancer

The article by Drs. Jones, Leak, and Muss is a timely review of some of the issues we face as oncologists sorting through our increasing numbers of older women patients with newly diagnosed breast cancers. The authors focus on data documenting a much smaller improvement in breast cancer–specific survival over time in women older than 75 years of age, compared with somewhat younger women, and they offer guidance to the reader in assessing both the comorbidities and breast cancer treatment options in this older age group.

Clearly the judgment calls of avoiding aggressive breast cancer–specific treatment in an elderly patient with many comorbidities who is likely to die of those other existing health issues, modifying “standard” adjuvant treatment for an older woman with some health issues, and treating very healthy older patients with effective treatment regimens largely proven superior in trials involving mostly younger patients, are difficult ones; they requires an evaluation process quite different from that which we likely use for a 40-year-old patient. While most of my comments will be directed at adjuvant radiation therapy issues after breast surgery, I will offer some general observations as well.

First, in their review Jones et al describe two 75-year-old patients, “A” and “B.” I believe a 75-year-old patient “C” also exists: someone who has many pre-existing comorbid conditions. Unlike “A” and “B,” who were appropriately screened, even offering patient “C” screening in the first place makes little sense if she cannot undergo a course of effective treatment for her breast cancer.

For appropriate older women, however, screening provides a benefit in this age group by identifying early-stage breast cancer. A recent article by Schonberg et al used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to identify women 67 years of age and older with newly diagnosed invasive breast cancer or ductal carcinoma in situ (DCIS), from 1992 through 2003. The authors then took a random 5% sample of Medicare beneficiaries living in the same geographic areas, without a breast cancer diagnosis. This group of women was age-matched to the breast cancer population by birth year, cancer location, and date of diagnosis. The match groups were in the following subsets: women aged 85 years and older, women 74 to 84 years old, and those 67 to 84 years old. The goal of the study was to compare survival by stage of breast cancer, using multivariable proportional hazards models to adjust for age at diagnosis, comorbidity, prior screening mammogram use, and sociodemographics.[1]

The results of the Schonberg study, with a median follow-up time of 7.8 years, demonstrated that women with either DCIS or stage I breast cancer had a mortality rate similar to that of the control group. Only in women with stage II or higher breast cancer was an increase in mortality seen when compared with the control group. Of note, in both stage I and stage II disease, “the risk of mortality compared with controls increased with receipt of less aggressive treatment.” The study also found that the relationship of “nonstandard treatment with mortality was smaller for women age 80 years and older than women age 67 to 79 years.” This study included 64,894 patients and the same number of controls.[1]

The Schonberg data support the hypothesis of Jones et al that the disparities in improvement of breast cancer survival in the elderly, compared with younger women, are related in part to use of less aggressive vs “standard” breast cancer treatments. These data for older women with DCIS or stage I breast cancer, who had the same survival rates as the control group, also support a need to continue to screen the older healthy patient.

Moving to the discussion of effective local-regional treatment in this age group, for older women presenting with stage II disease or higher, my recommendations for adjuvant radiation are similar to the recommendations that I give to my younger patients, provided the patient can tolerate the treatment process. For the older patient with stage I, hormone receptor–negative disease, I recommend whole-breast radiation after breast-conservation surgery. I offer all these women whole-breast hypofractionation, or a shorter, 16-visit course of treatment, based on several large prospective randomized studies showing identical outcomes compared with a 5-week course.[2-5] Assuming the surgeon has obtained negative surgical margins, I do not use a radiation boost in this age group, based again on a large randomized trial showing that it yields no significant improvement in local control in women over the age of 50 years.[6] So the treatment course becomes much shorter, and I find the women generally tolerate the radiation well.

For stage I hormone receptor–positive disease, as a coauthor of the Cancer and Leukemia Group B (CALBG) “Elderly Trial,”[7] I believe in and discuss the results of the trial, although I tend to encourage the healthy patient under age 75 to undergo radiation as well as endocrine treatment, since the updated results of this trial continue to show a decreased local recurrence rate in the radiation arm. I also discuss the scenario of hormone intolerance, or hormone aversion. To some women, the idea of taking a “pill” for 5 years has no appeal, and results from radiation alone in this age group are excellent.[8]

Finally, for cases in which the decision seems really “tough,” the 21-gene Oncotype Dx score has been shown to predict for local recurrences in node-negative women, in a recent National Surgical Adjuvant Breast and Bowel Project (NSABP) data set[9]; the use of this tool should be considered along with the grade and tumor size as suggested by Jones et al, to help in the decision-making process for local-regional radiation.

In summary, the “Tough Decisions-High Stakes” era is with us now; thoughtful and patient-sensitive screening and treatment guidelines specific for this age group are needed, and the review by Jones et al is a great start.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

References

1. Schonberg MA, Marcantonio ER, Ngo L, et al. Causes of death and relative survival of older women after a breast cancer diagnosis. J Clin Oncol. 2011;29:1570-7.

2. Bentzen SM, Agrawal RK, Aird EG, et al. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008;9:331-41.

3. Bentzen SM, Agrawal RK, Aird EG, et al. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008;371:1098-107.

4. Yarnold J, Ashton A, Bliss J, et al. Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial. Radiother Oncol. 2005;75:9-17.

5. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362:513-20.

6. Jones HA, Antonini N, Hart AA, et al. Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial. J Clin Oncol. 2009;27:4939-47.

7. Hughes K, Schnaper L, Cirrincione C, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 or older with early breast cancer. J Clin Oncol. 2010;28(15S): abstr 507.

8. Kantorowitz DA, Poulter CA, Sischy B, et al. Treatment of breast cancer among elderly women with segmental mastectomy or segmental mastectomy plus postoperative radiotherapy. Int J Radiat Oncol Biol Phys. 1988;15:263-70.

9. Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010;28:1677-83.