breast cancer is the second most common cancer among women in the united states , with approximately 54,010 new cases of carcinoma in situ ( noninvasive cancer ) and 207,090 cases of invasive cancer diagnosed per year .
in addition , breast cancer is the second leading cause of cancer death in women , with about 39,840 deaths occurring per year.1 five - year survival rates vary by stage : the 5-year survival rate for patients with stage 0 through stage iia breast cancer ranges from 92 to 100% , while the 5-year survival rate for patients with stage iv metastatic breast cancer is approximately 20%.1 thus , the goal of therapy for invasive breast cancer is primarily palliative  that is , aimed at alleviating and controlling symptoms as well as improving quality of life.2 treatments in common use for invasive breast cancer include cytotoxic chemotherapy , hormonal treatments , and targeted therapies / biologics , which can be administered as single agents or in combination with each other.3 given that current chemotherapies have advantages or disadvantages relative to each other , it would be useful to understand how these influence patient preferences for treatment .
for example , one recent study evaluated preferences for health states associated with chronic lymphocytic leukemia treatments using the standard - gamble method.4 other studies have also examined patient preferences for select groups of chemotherapy toxicities.5,6 however , to date , no study has evaluated the importance of toxicities relative to other characteristics such as efficacy and administration .
conjoint analysis , which is increasingly being used in evaluating medical interventions , involves respondents making trade - offs among product features ( attributes ) such as mode of administration and risk of adverse events.7,8 the resulting data , or utilities , enable the assessment of the relative importance of each treatment attribute ; specifically , they show the influence that each attribute has on overall treatment preferences .
the goal of the present study was to use conjoint analysis to capture patient preferences for attributes associated with chemotherapies for invasive breast cancer . specifically , the survey aimed to assess the trade - offs that breast cancer patients are willing to make among chemotherapies according to different toxicity , regimen , and efficacy profiles .
this was a cross - sectional , internet - based survey assessing the chemotherapy treatment preferences of women with breast cancer .
all participants were women with united states residency ; at least 18 years of age ; had a diagnosis of stage i through iv breast cancer ; had received chemotherapy treatment within the past 5 years ; and provided informed consent and health insurance portability and accountability act- compliant authorization.9 participants completed the survey at home and worked at their own pace .
however , research team members were available via telephone or email to answer questions or provide technical help if necessary .
the study followed the tenets of the declaration of helsinki , and the protocol was approved by a commercial institutional review board ( independent irb ; plantation , fl ) .
this research was implemented following published methodological guidelines for conjoint studies.10 the survey design and analysis are detailed below .
twelve attributes of eight invasive breast cancer chemotherapy treatments were identified from a comprehensive literature review , the common toxicity criteria grading system , a detailed assessment of breast cancer forum discussions , and consultation with clinical experts .
these attributes included selected grade iii / iv toxicities , efficacy ( survival advantage ) , and regimen .
attributes were described in lay terminology so that they could be easily understood by patients .
each attribute was presented in different levels that represented the full range of possibilities across available breast cancer treatments .
based on the literature and clinician input , potential ranges for the incidence of each of the toxicities were identified , and these were used as the most favorable and least favorable levels , respectively .
this involves a hybrid approach , in which the data are collected in phases.11,12 the respondent completes the aca computer - assisted questionnaire , and the questionnaire is modified during the responding process on the basis of the respondent s previous choices .
thus the interview can focus on just those attributes that the respondent considers most important and those attribute levels regarded as most relevant . in the first phase , respondents were asked to rate the levels of each attribute in terms of acceptability on a 7-point scale , from 1 ,  not at all acceptable  , to 7 , 
the second phase ( paired comparison questions ) elicited treatment preferences by asking respondents to make trade - offs among attributes and choose from a pair of hypothetical treatments . in each of these questions , the profiles of two hypothetical treatments 
labeled simply chemotherapy a and chemotherapy b  were presented with different levels of the same three attributes ( no chemotherapies were named in the survey ) .
respondents used a 7-point scale to indicate not only their preference , but the strength of their preference ; response options ranged from  strongly prefer a  to  strongly prefer b  .
the profiles presented to respondents in this second phase were customized based on responses to previous questions .
the survey was pilot - tested with respect to wording and comprehension in a sample of four breast cancer patients ; no major changes were necessary .
the conjoint data were analyzed using sawtooth software ssi web ( v 6.4 ; sawtooth software , sequim , wa ) .
analysis of aca data involved the combination of the initial rating ( the acceptability questions in the first phase ) and the paired comparison questions .
specifically , using the information from the initial rating questions , prior utilities were calculated .
for example , desirability values 3 , 2 , and 1 would be converted to 1 , 0 , and 1 , respectively .
these initial estimates are part - worths , where within each attribute the values have a mean of zero , and differences between values are proportional to differences in desirability ratings or rank orders of preference . with respect to the paired comparison questions ,
a column vector was created for the dependent variable as follows : the respondents answers were zero - centered , where the most extreme lowest value was given 4 , and the most extreme highest value was + 4 .
each pair s question contributed a row to both the independent variable matrix and dependent variable column vector .
ordinary least - square estimates of the n attribute levels were computed by regression of the dependent variable column vector on the matrix of independent variables .
the part - worth estimates based on the prior and paired comparison phases were normalized to have equal sums of differences between the best and worst levels of each attribute across all attributes .
the two vectors of part - worths were added together , yielding final utilities for each attribute level for each respondent .
the absolute values of the final utilities were arbitrary ; what was important was the magnitude of difference between them .
whereby the utility weight of the attribute level falling in the middle had a value that approximated zero and the more favorable level was higher , or positive , and the less favorable level was lower , or negative .
finally , the bayes approach was applied to the data to further refine the precision of the utility estimates .
the utilities enable the calculation of the relative importance of each attribute for each respondent in influencing treatment decisions .
specifically , the relative importance was calculated for each respondent by dividing the range for each attribute ( utility of highest level  utility of lowest level ) by the sum of ranges of all attributes for the respective individual and multiplying it by 100 .
these estimates indicate how much the difference in importance between the best and worst levels of each attribute affects the decision to choose a treatment .
these are ratio data , meaning for example that an attribute with an importance of 10% is twice as important as an attribute with an importance of 5% . using the mean utility weights for the attribute levels
, we compared the percentages of patients who would prefer the following scenarios differing with respect to selected attributes , while holding all other attributes constant : ( 1 ) three levels of efficacy ( no additional survival , 1 month additional survival , and 3 months additional survival ) ; ( 2 ) three regimens ( most convenient [ oral ] , least convenient [ 21-day cycle ; 3-hour infusion on days 1 , 8 , and 15 ] , and one in between [ 28-day cycle ; 610 minute infusion on days 1 , 8 , and 15 ] ) ; and ( 3 ) a 0% versus a 10% chance of each toxicity .
twelve attributes of eight invasive breast cancer chemotherapy treatments were identified from a comprehensive literature review , the common toxicity criteria grading system , a detailed assessment of breast cancer forum discussions , and consultation with clinical experts .
these attributes included selected grade iii / iv toxicities , efficacy ( survival advantage ) , and regimen .
attributes were described in lay terminology so that they could be easily understood by patients .
each attribute was presented in different levels that represented the full range of possibilities across available breast cancer treatments .
based on the literature and clinician input , potential ranges for the incidence of each of the toxicities were identified , and these were used as the most favorable and least favorable levels , respectively .
this involves a hybrid approach , in which the data are collected in phases.11,12 the respondent completes the aca computer - assisted questionnaire , and the questionnaire is modified during the responding process on the basis of the respondent s previous choices .
thus the interview can focus on just those attributes that the respondent considers most important and those attribute levels regarded as most relevant . in the first phase , respondents were asked to rate the levels of each attribute in terms of acceptability on a 7-point scale , from 1 ,  not at all acceptable  , to 7 ,
the second phase ( paired comparison questions ) elicited treatment preferences by asking respondents to make trade - offs among attributes and choose from a pair of hypothetical treatments . in each of these questions , the profiles of two hypothetical treatments  labeled simply chemotherapy a and chemotherapy b  were presented with different levels of the same three attributes ( no chemotherapies were named in the survey ) .
respondents used a 7-point scale to indicate not only their preference , but the strength of their preference ; response options ranged from  strongly prefer a  to  strongly prefer b  .
the profiles presented to respondents in this second phase were customized based on responses to previous questions .
the survey was pilot - tested with respect to wording and comprehension in a sample of four breast cancer patients ; no major changes were necessary .
the conjoint data were analyzed using sawtooth software ssi web ( v 6.4 ; sawtooth software , sequim , wa ) .
analysis of aca data involved the combination of the initial rating ( the acceptability questions in the first phase ) and the paired comparison questions .
specifically , using the information from the initial rating questions , prior utilities were calculated .
for example , desirability values 3 , 2 , and 1 would be converted to 1 , 0 , and 1 , respectively .
these initial estimates are part - worths , where within each attribute the values have a mean of zero , and differences between values are proportional to differences in desirability ratings or rank orders of preference . with respect to the paired comparison questions ,
a column vector was created for the dependent variable as follows : the respondents answers were zero - centered , where the most extreme lowest value was given 4 , and the most extreme highest value was + 4 .
each pair s question contributed a row to both the independent variable matrix and dependent variable column vector .
ordinary least - square estimates of the n attribute levels were computed by regression of the dependent variable column vector on the matrix of independent variables .
the part - worth estimates based on the prior and paired comparison phases were normalized to have equal sums of differences between the best and worst levels of each attribute across all attributes .
the two vectors of part - worths were added together , yielding final utilities for each attribute level for each respondent .
the absolute values of the final utilities were arbitrary ; what was important was the magnitude of difference between them .
whereby the utility weight of the attribute level falling in the middle had a value that approximated zero and the more favorable level was higher , or positive , and the less favorable level was lower , or negative .
finally , the bayes approach was applied to the data to further refine the precision of the utility estimates .
the utilities enable the calculation of the relative importance of each attribute for each respondent in influencing treatment decisions .
specifically , the relative importance was calculated for each respondent by dividing the range for each attribute ( utility of highest level  utility of lowest level ) by the sum of ranges of all attributes for the respective individual and multiplying it by 100 .
these estimates indicate how much the difference in importance between the best and worst levels of each attribute affects the decision to choose a treatment .
these are ratio data , meaning for example that an attribute with an importance of 10% is twice as important as an attribute with an importance of 5% . using the mean utility weights for the attribute levels
, we compared the percentages of patients who would prefer the following scenarios differing with respect to selected attributes , while holding all other attributes constant : ( 1 ) three levels of efficacy ( no additional survival , 1 month additional survival , and 3 months additional survival ) ; ( 2 ) three regimens ( most convenient [ oral ] , least convenient [ 21-day cycle ; 3-hour infusion on days 1 , 8 , and 15 ] , and one in between [ 28-day cycle ; 610 minute infusion on days 1 , 8 , and 15 ] ) ; and ( 3 ) a 0% versus a 10% chance of each toxicity .
of 121 participants who completed the conjoint survey , 108 ( 89% ) were included in the final data analysis .
thirteen participants were excluded because their responses in the first section of the survey were illogical ( eg , a participant rating a 24% chance of fatigue as more acceptable than a 0% chance ) in at least two instances .
table 2 reports the demographic and clinical characteristics of the study population who were included in the analysis .
the mean age was 50 years , with a mean time of 80 months since cancer diagnosis ; 60% had attained at least a college - level education .
with respect to treatment experience , about 35% of patients were on chemotherapy at the time of their participation in the study , and the mean time since the sample s last chemotherapy administration was approximately 19 months .
the mean utilities for each attribute level are presented in table 3 ( the actual values are arbitrary ; the magnitude of the differences among them are what should be evaluated ) . in general
, the utilities for each attribute level were ordered in the direction that was expected , where the most favorable attribute level had the highest utility and the least favorable level had the lowest .
the efficacy attribute had the highest utility value for its most favorable level (  additional survival benefit of 3 months  ) and lowest utility value for its least favorable level (  no additional survival benefit  ) , with means of 97.05 and 83.77 , respectively .
this finding indicates that patients view a change in survival advantage from 0% to 3 months as more important than a change from the least favorable to the most favorable level for all other attributes .
overall , the most important attributes in driving treatment preferences were survival advantage , neutropenia / hospitalization , and toxicities such as nausea / vomiting , fatigue , and diarrhea .
least important attributes were the toxicities of mucositis / stomatitis , myalgia , and hand - foot syndrome .
in general , the difference between the most inconvenient to the most convenient administration regimen was less important than a 13% chance or more of severe toxicities , but more important than a 10%12% chance of severe toxicities .
the exception to this finding was myalgia , which had a maximum level of 15% chance of occurring ; the difference between 0% versus 15% chance of myalgia was still less important than the difference between the most inconvenient and most convenient regimen ( percentage importances = 8.8% versus 3.2% ) . in sensitivity analyses , we created scenarios for each toxicity ( ie , each attribute that was a side effect ) in which we compared preferences for a 0% risk of that toxicity versus a 10% risk of that toxicity , holding the risk of all other toxicity attributes constant .
specifically , we obtained preference estimates for two product profiles in which one toxicity differed by 10% and the remaining attributes were held constant ; we repeated this for each side effect .
figure 2 shows the percentages of patients who would prefer a treatment given a 0% chance versus a 10% chance of each toxicity occurring .
the findings show that patients most preferred to avoid neutropenia / hospitalization , diarrhea , nausea / vomiting , and sensory neuropathy ( ie , they most preferred no risk of these toxicities relative to no risk of the other toxicities ) .
an additional analysis found no substantial differences in relative importance estimates of toxicities between those who had experienced the side effect versus those who had not ( data not shown ) .
figure 3 presents the percentages of patients preferring each of three regimens that differ in efficacy ( survival advantage ) and the percentages of patients preferring three regimens , ie , an oral regimen , a regimen somewhat in  the middle  with respect to convenience ( 28-day cycle ; 610 minute infusion on days 1 , 8 , and 15 ) , and the most inconvenient ( 21-day cycle ; 3-hour infusion on days 1 , 8 , and 15 ) .
the findings show that the difference between a 1-month and 3-month survival advantage substantially influenced patient preferences ; the percentages of patients preferring each of these regimens increased from 5.7% to 93.7% , respectively .
also , an oral regimen was highly preferred ; 76.6% of patients would choose an oral regimen versus 18.9% who would choose the  middle  regimen .
to the best of our knowledge , this study is the first to assess patient preferences for invasive breast cancer treatments considering a variety of treatment features . specifically , this study assessed the trade - offs that breast cancer patients are willing to make among the risks of severe toxicities , administration regimen , and efficacy when choosing a chemotherapy . among the chemotherapy attributes evaluated in this study , those that were most influential in driving patient preferences for treatment were improved survival , the risk of neutropenia leading to hospitalization , and the risks of severe fatigue , nausea and vomiting , and diarrhea .
least important were the risks of severe myalgia , mucositis , and hand - foot syndrome .
the study findings are useful in better understanding patient preferences in oncology and may enhance the medical decision - making process .
for most patients , the difference between having no additional survival advantage and having a survival advantage of 3 months was about three times more important than an approximate 10% versus 0% risk of experiencing several severe toxicities , including severe myalgia , mucositis , hand - foot syndrome , and motor neuropathy .
in addition , the incremental improvement in survival was one - and - a - half times as important as an approximate 15%20% versus 0% risk of having severe nausea and vomiting , fatigue , diarrhea , or sensory neuropathy .
the finding of the high relative importance of improved efficacy is consistent with previous conjoint analyses of medical therapies13,14 and a review of previous literature,15 which found that patients are willing to accept the risk of serious adverse events in exchange for improved efficacy .
for example , johnson et al12 evaluated the treatment perceptions among patients with multiple sclerosis , and they found that most patients indicated they are willing to accept risks of life - threatening adverse events in exchange for improvements in their health outcomes .
this study builds upon previous work that has examined rankings among chemotherapy side effects.16 specifically , sun et al16 evaluated preferences for 27 different side effects among patients with ovarian cancer .
they found that severe nausea and vomiting was the least preferred toxicity and that  numbness in hands / feet 
similarly , the current study showed that patients would most want to avoid the chance of severe nausea and vomiting and the chance of severe numbness in the arms and legs ( sensory neuropathy ) among the various potential toxicities evaluated , assuming that they each had an equal chance of occurring .
our study found no substantial differences in the relative importance of toxicities between those who had experienced the toxicity versus those who had not .
this finding differed from a previous study that examined utility ( time trade - off ) estimates for chemotherapy - related ototoxicity , nephrotoxicity , and neurotoxicity among ovarian cancer patients.17 specifically , the study found that the most favorable assessment of a particular toxicity was reported from individuals who experienced the selected toxicity .
this may be attributable to the fact that patients were asked to assume that the toxicity was permanent ; as such , patients with experience may have felt they could better tolerate the effect than nave patients .
in contrast , in the current study , each of the side effects had a specified duration , and thus this may not have been significant enough to translate into differences between those experienced versus not experienced with each toxicity .
moreover , our findings were consistent with the finding of no substantial differences observed in relative importance of eleven of 12 side effects between hiv treatment - experienced , who may have experienced treatment side effects , versus treatment - nave patients.18 the current study also found that a more convenient administration regimen was more important to patients than severe side effects when the respective risk was less than 13% .
similarly , improved convenience has been found to be influential in treatment choices in other studies.13,14 for example , in a study of patients with idiopathic thrombocytopenic purpura , patients were willing to accept significant treatment - related risks in exchange for improvements in treatment efficacy and convenient administration.13 our study was not without limitations .
first , each of our toxicity attributes was described using durations from a few days to 6 months after treatment end , and these durations represented clinical averages .
these average durations may not be reflective of individual experiences , however , as our discussions with clinicians revealed that side effect experience is highly variable between patients . in addition , the participants in our sample did not represent the full range of breast cancer patients ; the majority were well - educated , most were caucasian , and they were all healthy enough to complete a computer - based survey at home .
it is unclear whether the preferences of severely ill cancer patients ( eg , those who are bedridden ) or other ethnic groups would be different from those expressed by patients in our sample . because of these limitations , while our study has yielded important findings with implications for the medical community , future research is necessary to evaluate the generalizability of our conclusions .
in summary , this survey evaluated a comprehensive set of severe toxicities and other features that are observed with chemotherapies for invasive breast cancer .
our study showed that , despite the risk of serious toxicities , a small incremental survival advantage is highly influential in patient preferences for chemotherapy .
the findings from this research may be useful in incorporating patients views into medical decision making processes , patient education , cost resource allocations , and drug development .
a better understanding of patients preferences may help to improve patient satisfaction and compliance with treatment regimens .
 backgroundtherapies for invasive breast cancer may be associated with an incremental survival advantage that should be weighed against the risk of toxicities when making treatment decisions . 
 the objective of this study was to elicit patient preferences for a comprehensive profile of attributes associated with chemotherapies for breast cancer.methodsthis was a cross - sectional study of 121 patients with stage i - iv breast cancer who completed an internet - based conjoint survey that assessed the following attributes : ten grade iii / iv toxicities , survival advantage , and administration regimen . literature and expert input were used to identify descriptions for each attribute and respective levels ( eg , different risks of toxicities ) . 
 subjects rated the attribute levels on a series of scales and indicated preferences in pair - wise comparisons of two hypothetical treatments differing in attribute levels . 
 ordinary least - squares regression was used to calculate utilities ( preference weights ) for each attribute level.resultsof the twelve attributes , survival was the most important ; specifically , a survival advantage of 3 months versus no survival advantage was most influential in the perceived value of chemotherapy . among toxicities , 
 the differences in the risks of neutropenia with hospitalization , diarrhea , nausea , and fatigue had the most impact on preferences ; the risk differences of myalgia , stomatitis , and hand - foot syndrome had the least . 
 in general , a more convenient administration regimen was less important than a 13% chance or more of severe toxicities , but more important than a 10%12% chance of severe toxicities.conclusionbreast cancer patients place high value on small incremental survival advantages associated with treatment despite the risk of serious toxicities . 