Is Age Still the Deciding Factor? Commentary on “The Effect of Age on Delay in Diagnosis and Stage of Breast Cancer” by Partridge et al.

Young breast cancer patients face multiple different challenges when diagnosed and when undergoing treatment for breast cancer than do postmenopausal patients. Very young breast cancer patients, especially those aged 35 years, have been described in multiple reports to have a worse prognosis [1–3]. Additionally, because women are not routinely recommended to consider initiating screening mammography until their 40s or 50s, a younger woman is more likely to develop a cancer at an advanced stage and to be diagnosed because of the onset of symptoms. There remains concern that a delay in diagnosis of breast cancer in a younger woman is one of the contributing factors to these worse outcomes in young breast cancer patients. It was estimated by the American Cancer Society that 5% of cases of breast cancer will be diagnosed each year in women aged 40 years [4]. Several case series have demonstrated worse outcomes in younger breast cancer patients. Nixon et al. [1] reported on 107 patients aged 35 years with either stage I or stage II breast cancer and compared them with their older counterparts. The younger patients were found to have a statistically significant greater recurrence risk and risk for developing distant metastatic disease. Kroman et al. [3] reported that younger women who had node-negative cancers or tumors 2 cm were significantly more likely to die from their cancer if they did not receive systemic adjuvant therapy. However, this effect was mitigated if they received cytotoxic therapy. Race may also play a factor in the diagnosis of breast cancer in young women. Black women have a twofold higher chance of being diagnosed at 35 years of age than white females. In addition, black women have higher presenting stages and higher mortality rates from breast cancer in the U.S. than white women [5, 6]. When looking at the underlying biology of younger women with breast cancer, the majority of reports show a higher rate of hormone receptor–negative tumors [1–3] than in postmenopausal breast cancer patients. When evaluating very low-risk disease, such as node-negative tumors that are 1 cm, age was identified as an independent risk factor for the recurrence-free survival interval. This was more significant in women with human epidermal growth factor receptor (HER)-2 and hormone receptor–positive tumors and was not demonstrated to be significant in patients with triple-negative tumors [7]. Additionally, Anders et al. [8] used microarray data from 784 women with early-stage breast cancers, again demonstrating lower percentages of hormone receptor positivity and higher grade tumors. There were 367 gene sets found to significantly differentiate the tumors arising in younger women from those in older women. Examples of gene sets that were differentiated by age included those encoding epidermal growth factor receptor and mammalian target of rapamycin as well as BRCA1, among many others [8]. This information was particularly intriguing and hypothesis generating regarding combination therapy that could take advantage of such pathways in younger breast cancer patients. Therefore, the question remains, is it truly the age of the patient herself that is the underlying cause of this described worse prognosis or is age just a surrogate marker for more aggressive tumor subtypes that occur more frequently in younger patients? Another confounding factor in this debate is the question surrounding a delay in diagnosis. There have been conflicting reports on whether or not a delay in diagnosis and a delay from