While the use of complementary and alternative medicine (CAM, including herbal remedies), has increased among the general population [1]. CAM use still remains more common among cancer patients [2]. Among cancer patients, breast cancer patients remain as the most likely users of CAM [3]. The prevalence of CAM among cancer patients varies based on different CAM definitions [4, 5]. Richardson et al. reported that as many as 83% breast cancer patients use at least one type of CAM [6]. The leading reasons why breast cancer patients use CAM include improving their quality of life (QOL), aiding their conventional medical treatment for cancers, preventing their cancer recurrence, and eventually extending their lifespan [7, 8]. However, few scientific data exist on survival or QOL in relation to CAM use, especially herbal remedy use, among long-term breast cancer survivors.

The relationship between CAM or herbal remedy use and cancer patients' survival has rarely been studied. One Norwegian study following 252 patients with a mix of different cancers for 5 years reported that CAM use had no impact on mortality [9]. Another Norwegian study following 515 patients with different types of cancer for 8 years found that CAM users had a 30% higher mortality risk (P = 0.056) during the follow-up period than non-CAM users [10]. Neither study provided data specifically for breast cancer patients.

Most previous studies that evaluated CAM or herbal remedy use by patients in relation to QOL were conducted within 5 years of their initial diagnosis [11–14]. Recently, long-term breast cancer survivors' QOL has started to attract attention from researchers [15–17]. Such research is needed, especially given that early detection and efficacious adjuvant systemic therapy of breast cancer have improved the likelihood of long-term survival. Based on the data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, the proportion of patients with stage I (T1a,bN0M0) breast cancer diagnosed between 1988 and 2001 who remain alive at 10 years post-diagnosis is 76% [18]. Younger women who become long-term survivors commonly experience late health effects of treatment, symptoms associated with a deficit of estrogen, fear of recurrence, problems with sexuality, and poorer mental health and psychologic distress [15, 17]. In a survey on beliefs about the roles of CAM use conducted among long-term breast cancer survivors (on average, 8.7 year post-diagnosis), more than 50% believed that CAM use would prevent cancer recurrence (69%), play a more active role in recovery (67%), and help to manage stress (64%) [19] although thus far, few scientific data exist to support these beliefs.

We previously reported that, among women who were long-term (> 10 years) breast cancer survivors and aged 40 years or younger when initially diagnosed, herbal remedy users had a lower mental component summary score on the Medical Outcomes Study Short Form-36 (SF-36) questionnaire than non-users, but herbal remedy users and non-users did not differ on the SF-36 physical component summary scores [20]. In our previous report, QOL and herbal remedy use information were collected at the same point in time and we were thus not able to determine whether herbal remedy use is associated with later QOL. However, additional follow-up data on these patients' QOL collected 2-5 years after the initial collection of herbal information now affords us the opportunity to evaluate whether herbal remedy use at baseline is associated with the changes in SF-36 QOL measures between the two surveys. Furthermore, the extended follow-up data on women's survival from baseline (1999-2000) through 2007 provides the opportunity to explore whether herbal remedy use at baseline is associated with mortality among long-term breast cancer survivors. In this report, we examined whether herbal remedy use is associated with survival or the health-related QOL of these long-term breast cancer survivors.

Herbal remedy use was associated with non-statistically significant increases in the risks for all-cause and breast cancer mortality. Both herbal remedy users' and non-users' mental component summary scores on the SF-36 increased similarly from the first survey to the second survey, but herbal remedy users' physical component summary scores decreased more than those of non-users.

This study has several important limitations which may affect the results we observed. First, although our results were obtained from a prospective study of young breast cancer patients who had survived more than 10 years, 276 (37%) breast cancer patients had died by the time we initiated this study, so that participants were more likely to be a select group of healthy women who were long-term survivors. Thus, our findings may not be generalizable to all breast cancer patients, but they do provide important information regarding long-term survivors of breast cancer who were diagnosed at a young age. Second, herbal remedy use, as measured in our study, represents use during a six month time period beginning, on average, 12.5 years after breast cancer diagnosis. We did not collect information regarding the timing of initiation of herbal remedy use, duration or frequency of use or reasons for use. Herbal teas were commonly used herbal remedies among our study population, but we did not collect the components of herbal teas or brand of herbal teas or whether any additives had been added to herbal teas to alter color or taste. Third, we relied on self reported information on herbal remedy use. Errors in reporting use of herbal preparations are possible. However, we worded questions carefully, mailed scales and questionnaire items in advance of the telephone interview to enhance comprehension and consistency of reporting, and limited the questions to recent herbal remedy usage (within the past six months of interview). Fourth, among 33 women who died from breast cancer during our follow-up for survival, 27 had post-diagnosis cancer-related conditions including two who had a contralateral breast cancer by the time of our baseline telephone interview. Unfortunately, we were unable to collect this information throughout the follow-up for survival. Therefore, we cannot rule out the possibility that women might have died of a new breast cancer rather than their first primary breast cancer. Fifth, due to the relatively small number of participants, we only assessed the effects for overall herbal remedy use and three commonly used herbal remedies. We were unable to explore the effects for those having a lower frequency of use among our participants. In fact, even for overall herbal remedy use, the small number of deaths led to insufficient statistical power to detect small or moderate differences in mortality risk between herbal remedy users and non-users. Due to the same limitation, our main exposure variable, herbal remedy use, grouped all types of herbal remedies. The definition of herbal remedy use was therefore non-specific. Finally, six of forty P values we reported here for testing the roles of herbal remedies in quality of life reached statistical significance (P ≤ 0.05); we did not adjust for multiple comparisons as, with the relatively small number of participants, these analyses were consider as exploratory.

Our data show that herbal remedy use tended to be associated with a poor survival among long-term breast cancer survivors although the associations did not reach statistical significance, due to the small number of deaths and further deaths could alter the direction of findings. Our findings are consistent with a Norwegian study which followed 515 patients with a variety of cancers for up to 8 years and showed that CAM use was associated with poorer survival; 79% of CAM users died during follow-up compared with 65% of nonusers [10]. However, a second Norwegian study which followed 252 patients with heterogeneous cancers for up to 5 years did not find any association between CAM use and mortality [9].

Our data also showed that herbal remedy users' physical component summary scores decreased more than those of non-users between the first and second surveys. Most previous studies that have evaluated CAM or herbal remedy use in relation to QOL were conducted among patients within 5 years of initial diagnosis [11–14]; however, one study evaluated CAM use in a large sample of women who were diagnosed from 5 to 10 years earlier [16] and our prior report for this study population assessed the association between CAM use and QOL concurrently among 10-16 year survivors [20]. Among these studies, one found that CAM users (either all CAM or herbal CAM) had poorer physical and mental health function than non-users [11]; three showed poorer mental health function among CAM users compared to non-users [12, 16, 20], but not physical health function. A study conducted among Chinese breast cancer survivors found no association between any Chinese herbal medication use and perceived overall QOL [13]. However, in all but one study [12], the information on health-related QOL was collected at the same point in time as CAM use was collected. The study [12], which assessed QOL after CAM use, was able to determine if CAM use had been initiated prior to breast cancer treatment or subsequent to it, but covered only the 12 month period following initial diagnosis.

Reasons are unclear for our observation that herbal remedy use was associated with a poorer survival or greater decline in physical health summary scores between our two surveys. A recent published Norwegian study investigating CAM use in 735 cancer patients who had survived 5 years or more after breast cancer diagnosis, found CAM use initiated after diagnosis was associated with a poor prognosis suggesting that CAM might be used by those with less hope of a cure by conventional therapy [29]. Although no published data directly indicated that CAM use is associated with a lower score of QOL measures in the general population, previous data have shown that substantial amount of CAM use can be attributed to poorer health or the treatment of existing chronic health conditions [1, 30–32]. Based on a national telephone interview survey conducted in the United States in 1997, 42% of all alternative therapies were used exclusively to treat existing illness [1]. Among breast cancer patients in one study, a variety of symptoms (treatment side effects as well as other health and cancer-related problems) have been positively related to the initiation of CAM use [12]. We found that herbal remedy users in our study were more likely to have comorbidities at the baseline interview assessment. The poorer survival and greater decrease in physical component summary scores among herbal remedy users may have resulted from poorer health motivating the use of remedies to alleviate symptoms although we controlled for comorbidities when comparing herbal remedy users and non-users. The differences in both survival and in the SF-36 physical component score between herbal remedy users and non-users remained when analyses were restricted to women without any comorbidities considered in our study.

We also considered that the lower physical QOL scores of the herbal remedy users might result from some of the users opting out of conventional therapy for breast cancer. Therefore, we adjusted for types of initial treatments (both surgical and non-surgical) in our analyses. Based on previous studies, approximately 5-12% of cancer patients may abandon appropriate therapy and pursue alternative treatments [33, 34]; yet in most cases, alternative medicine is used to complement rather than replace conventional therapy [12, 33, 34].

It is possible that herbal remedy use could have interfered with chemotherapy treatment by inhibiting some enzymes in the cytochrome P450 (CYP) family, such as CYP1A2, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 [35, 36] if this use was initiated soon after diagnosis. This might explain the poorer survival and greater decline in physical health summary scores among herbal remedy users. However, as our participants were, on average, 13-year survivors, any potential interaction between chemotherapy treatment and concurrent herbal remedy use would not be expected to persist. Therefore, the associations that we observed in the current data need to be verified in the future studies with a larger sample size.

Our data provide some evidence that herbal remedy use is associated with a poorer survival and a poorer physical component score for health-related QOL among long-term (> 10 years) breast cancer survivors. These conclusions are based on the exploratory data from a prospective study using two-sided statistical tests with no correction for multiple testing and are limited by the few deaths for the survival assessment and the lack of information regarding the timing of initiation of herbal remedy use or duration or frequency of, or reasons for herbal remedy use. The potential roles for herbal remedies in breast cancer patients' survival and QOL merit further exploration.