Young Age.

Most patients in whom the diagnosis of breast cancer is delayed are young, with a median age of 42 years. In Kern’s previous 20-year review of the delayed diagnosis of breast cancer, 45 cases of breast cancer malpractice litigation tried in the US federal and state civil court system between 1971 and 1990 were critically analyzed. In 21 cases in which a patient’s age could be identified, the patients were young, with a mean age of 40 years (range, 22 through 59 years). When cases were grouped by 10-year intervals, the ages of patients were as follows: 4 (19%), 20 to 29 years; 8 (39%), 30 to 39 years; 5 (30%), 40 to 49 years; and 4 (19%), 50 to 59 years. Of the patients with known ages, 4 (19%) were younger than 29 years of age; 11 (52%), younger than 39 years of age; 16 (76%), younger than 49 years of age; and all patients younger than 59 years of age. The menopausal status of the patients was identified in 25 (55.5%) of cases. Of these 25 women, 68% were hormonally active, 15 (60%) were known to be premenopausal, and 2 (8%) were pregnant. Postmenopausal women made up only 5 (11.1%) members of the group. The PIAA 1995 Breast Cancer Study noted the average age of misdiagnosed patients was 46 years, an increase of 2 years over the average age of 44 years reported in their previous 5-year study.

More current claims studies have continued to demonstrate the extraordinarily young age of misdiagnosed breast cancer patients. In the 2013 PIAA claims review of 2157 cases, the median age range was 40 to 49 years, which constituted 32.7% of all cases. Patients aged 30 to 39 comprised 15.9% of cases, and those under age 30 comprised 4.1% of cases. Those patients 50 to 59 years accounted for 26.3% of cases, followed by those 60 to 69 years (11.6% of cases), with those greater than 70 years of age comprising 4.9% of cases.

Perhaps the most important finding from my Kern’s medicolegal study was that misdiagnosed breast cancer patients are on average 20 years younger than the median age of breast cancer patients in the US SEER/NCI database, which is 63 years. This same finding of misdiagnosed patients being younger than those reported in cancer databases holds true for other types of misdiagnosed cancer as well. Fig. 86.5 illustrates the age differential in misdiagnosed cancer patients from our study of delayed diagnosis in 13 different organ sites. For all organ sites, a delayed diagnosis occurred in patients at a younger age than the typical age of presentation in the SEER population. The difference in median ages between diagnostic delays and the SEER database ranged from 8 to 27 years. On average, patients with diagnostic delays were younger than SEER patients by 16.2 years (standard error, 2 years).

Line chart comparing the ages of patients with misdiagnosed cancer in nine organ sites with the median age of patients presenting with cancer derived from the Surveillance, Epidemiology, and End Results (SEER) Reporting Program of the National Cancer Institute database. Patients receiving a delayed diagnosis of cancer are younger than the median age for cancer in the SEER population, by intervals ranging from a minimum of 8 years (male reproductive cancer) to a maximum of 27 years (female reproductive cancer). For the delayed diagnosis of breast cancer, the difference in age between those misdiagnosed and the SEER population is 21 years. This age differential is called a litigation gap because it is the most common cause of misdiagnosis leading to malpractice litigation. GI, Gastrointestinal.

(From Kern KA. The anatomy of surgical malpractice claims. Bull Am Coll Surg. 1995;80:34-49.)

Kern refers to the age differential in misdiagnosed cancer as a litigation gap rather than an age gap, because the young age of cancer patients, in general, leads to delays in biopsy and specialized radiographic imaging, which often results to malpractice litigation. As it relates to breast cancer, other studies have confirmed these findings that misdiagnosed patients are younger than the typical population at risk. Diercks and Cady also confirmed a median age of 42 years for 57 patients in Massachusetts in whom the diagnosis of breast cancer was delayed. Max and Klamer studied 120 women younger than 35 years of age who had breast cancer. In this group of women, who had a mean age of 31 years, 9.1% were pregnant or lactating. Delays in diagnosis were common: in 7% of patients, physicians delayed more than 2 months before recommending a biopsy. In this study, 61% presented with a painless lump; mammography was done in 61% of patients, and in 52% of this group, mammography was negative. In 11% of patients, mammography was equivocal and did not lead to biopsy. Pregnancy-associated delays in diagnosis are discussed more completely later in this chapter but are mentioned here to emphasize the importance of young age as a cause of misdiagnosis. The average age of pregnant patients with breast cancer is 32 to 38 years. However, pregnant patients harboring breast cancer can be extremely young, and some have been described to be as young as 16 to 18 years of age. This is in contrast to nonpregnant patients, in whom breast cancer before age 20 to 25 is extraordinarily rare. In a series of 95 adolescent girls with breast masses, Hein and coworkers showed there were no breast cancers in these young women, who had an average age of 15.9 years (range 12–20 years). However, the authors noted two cases of cystosarcoma phyllodes.

The young age of patients with the delayed diagnosis of cancer is a unique aspect of negligence litigation in malignant disease. Generally, elderly women are more likely to sustain negligence-related, adverse medical events not related to breast cancer. For example, in one study, patients older than 64 years were twice as likely to experience legally compensable complications during hospitalization as patients younger than 45 years of age. Many physicians are unaware that nearly one-fourth of all breast cancer deaths occur in women whose age is not usually associated with the presence of breast cancer. Two percent of breast cancers occur in women between 15 and 34 years of age, 10% occur in those younger than 40 years of age, and 21% occur in women between 35 and 54 years of age. A recent study of the rates of breast cancer in women 30 years of age or younger with breast masses found the incidence of cancer was 2.5%. McWhirter calculated that each general practitioner in England is likely to see a case of breast cancer in women younger than 40 years of age only once in every 15 years of his or her working life.

Self-Discovered Breast Mass.

Palpable masses are often present in misdiagnosed women with breast cancer. In Kern’s civil court analysis of 45 cases of misdiagnosed breast cancer, definite physical findings were present in 82% (37 of 45) and included the following: painless mass, 64% (29 of 39); painful mass, 9% (4 of 45); and nipple discharge (bloody or green) or rash, 6% (3 of 45). Thus 73% of misdiagnosed breast cancer patients presented with a self-discovered breast mass. This finding was confirmed in a larger series of 127 breast cancer cases, in which 61% of patients presented with a breast mass. In the 1990 PIAA study of misdiagnosed breast cancer, the findings at physical diagnosis were reported. In 273 cases, 62.1% (159 of 273) presented with a mass without palpable axillary nodes, and 9.8% (25 of 273) presented with a mass and palpable nodes. Thus 72% of patients with delayed diagnosis of breast cancer originally presented to a physician with a self-discovered breast mass. Abnormal physical findings exclusive of breast masses were present in a smaller percentage of patients: 5.9% (15 of 273) presented with bleeding or nipple discharge, 3.5% (9 of 273) presented with palpable axillary nodes only, and only 16% (41 of 273) presented with no physical findings. Summing up these figures, 81.3% (208 of 273) of patients presented with a physical finding compatible with breast cancer. In these litigated cases, only 72.9% (199 of 273) of patients received a mammogram, only 19.8% (54 of 273) underwent a fine-needle biopsy or aspiration, and only 2.9% (8 of 273) received an ultrasound examination. These studies show that a physical abnormality was detected and was documented by physicians on initial presentation in more than three-fourths of patients in whom the diagnosis of breast cancer was delayed.

Unfortunately, the physical abnormalities detected initially in patients with misdiagnosed breast cancer are misinterpreted as benign disease, largely because further workups of these breast abnormalities are either inadequate (relying solely on mammography) or are not performed at all. From medicolegal studies as noted, Kern suggests that isolated, unilateral masses of the breast in women older than age 25, which, on ultrasound evaluation are either solid or are not simple cysts, receive a cytologic or histologic diagnosis (with FNA biopsy, core biopsy, or open excisional biopsy). Such lesions cannot be accurately diagnosed based on visual observation, physical examination, or mammography alone. Even ultrasonography without needle aspiration or biopsy has been accompanied by breast cancer malpractice litigation. In the 2013 PIAA claims study, 4% of cases (87 of 2157) involved diagnostic ultrasound that incorrectly diagnosed a malignant breast lesion as benign.

Unfortunately, before the definitive diagnosis of breast cancer is made in misdiagnosed patients, a benign label is applied to their breast condition, without attempts to obtain a histologic diagnosis. In 1992 Kern reported the prediagnostic labels for 29 cases of misdiagnosed breast cancer. The benign labels were as follows: fibrocystic disease was diagnosed in nine cases, a simple or premenstrual cyst was diagnosed in four cases, abnormal milk gland or galactocele was diagnosed in four cases, mastitis was diagnosed in four cases, a “hormonal” mass was diagnosed in four cases, and an intraductal papilloma was diagnosed in four cases. None of these diagnoses were confirmed by the results of biopsy.

Other studies have confirmed that palpable breast lesions presenting as isolated breast masses are commonly misdiagnosed. Nichols and coworkers, in a study of the National Health Service and breast cancer evaluation, reported that 25 of 57 women with discrete lumps were not referred immediately for evaluation. Many errors are related to the initial inability of a physician to palpate a mass detected by the patient. Deschenes and colleagues reported the high frequency of mislabeling of breast cancers in middle-aged women as benign fibroadenomas. Reintgen and associates studied the threshold of physical detection of breast cancers. From a study of 509 breast cancers at a university breast clinic, they determined the following: (1) the threshold of clinically detected breast cancer is 5 mm, (2) the median detection limit (50% of cancers detected) occurs at 11 mm, and (3) experienced clinicians do not detect more than 80% of breast cancers until the cancer is larger than 16 mm. Because the absolute threshold of detection of breast cancer by patients has never been specifically evaluated, one explanation for physician error in physical examination is simply that patients can detect breast masses at smaller sizes than physicians are able to detect.

False-Negative Mammogram.

The role of diagnostic mammography in women with symptomatic breast disease is a subject of controversy because it has been linked to the creation of diagnostic delays by physicians. This chapter does not address the issue of screening mammography in asymptomatic women, which has been shown through a variety of clinical studies to improve survival in women older than 50 years and perhaps those younger as well. Instead, this section addresses the question of failure to image symptomatic or palpable breast cancers.

Errors in reading mammograms include technical errors in 5%, observer errors in 30%, and nonimaging of breast tumors because of dense or dysplastic breast parenchyma. Nonimaging because of dense or dysplastic breast parenchyma is an age-related phenomenon and the greatest cause of mammographically associated delays in diagnosis. In most cases, diagnostic delays in women with symptomatic breast cancer are a result of false reassurance to physicians that the mammogram does not show breast cancer (i.e., false-negative mammography). Although the threshold size for detection of breast cancer (the minimum size required to consistently see the lesion) is thought to be approximately 2.3 to 2.6 mm, this applies to women with optimal breast tissue for imaging, which generally occurs in women older than 50 years of age. For women younger than 50 years of age, the threshold size of tumor visualization may be considerably greater; it may not be reached until 2 cm or greater, particularly in the youngest of women. Thus despite the presence of an obvious breast mass, the mammogram may show nothing suspicious. In such women, the cancer may have grown to a size allowing metastasis long before it can be imaged with modern mammography. By the time a tumor has reached only 2 mm in size, it contains 4 million cells and has undergone 22 net cell doublings. Tumor angiogenesis, a mandatory process before metastases can reach the systemic circulation, is thought to occur much earlier, at 13 net cell doublings or 0.3 mm in size. Tumor size alone, however, is not the sole determinant of metastases. The role of histologic determinants of prognosis and the future role of molecular genetic determinants of metastases remain central to any discussion regarding the timing of metastatic spread of disease. As yet, our understanding of the interaction between tumor growth, local nodal spread, and systemic spread of metastases is incomplete.

The high frequency of false-negative mammograms in middle-aged women with breast masses is unappreciated by many physicians. Although the false-negative rate for mammography is generally reported as being 7% to 20%, this figure applies to women older than 50 years of age; the actual false-negative rate increases greatly in younger women. For example, the false-negative rate of mammography approaches 80% in Kern’s studies. Other medicolegal studies have shown similar high false-negative rates of mammography. In both the 1995 and more recent 2002 PIAA studies of breast cancer lawsuits, 70% to 79% of diagnostic mammograms were falsely read as negative (or less commonly, equivocal results). Thus a breast mass was documented by physicians on initial presentation in almost three-fourths of patients. However, evaluation by physicians rarely proceeded beyond a negative mammogram, resulting in the delayed diagnosis of breast cancer.

In another study of women younger than 30 years of age with an isolated breast mass, 74% of these masses did not produce an image on mammography. In the Breast Cancer Detection and Demonstration Project involving 280,000 women, mammographic results were falsely negative in 36% of patients 40 years of age compared with 9% of women 75 years of age. Woods and coworkers reported that the average age of those with palpable breast lesions and false-negative mammograms was 44 years. This was significantly less than the average age of those with positive mammograms of 57 years. Mann and associates reviewed 36 women with palpable breast cancer and false-negative mammographic results. The average age of patients was 45 years. The subsequent delays in diagnosis ranged from 3 to 24 months. They noted that 52% of women younger than 45 years had normal mammograms despite a malignant breast mass. Bennett and colleagues reported a false-negative mammography rate in 227 women with symptomatic breast cancer of 24% (8 of 33 cancers). The reported delay caused by false-negative mammography was 8 months. Max and Klamer noted that 52% of mammograms were falsely negative in women younger than 35 years of age who had palpable breast cancers. Walker and Langlands and Walker, Gebski, and Langlands noted a false-negative rate of 30.7% in a group of 230 women with a median age of 50 years. The false-negative report led to a mean treatment delay of 12.7 months, ranging between 3 and 60 months. Joensuu and coworkers reported that the false-negative rate in women younger than 50 was 35% in a study of 306 women with invasive cancer. This was significantly different than the rate of 13% in women older than 50 years of age ( p < .0001). In those with a false-negative mammogram, 30% had delays of 6 months or more. For those with true-positive mammograms, no patients were delayed 6 months.

Others have reported that false-negative mammography is common in middle-aged women. Thus the woman with a breast mass who is 45 years of age or younger faces two perils in the diagnostic process. First, physicians assume that she is too young to have breast cancer. Second, given the difficulties inherent in imaging premenopausal breast tissue, mammograms may not provide useful diagnostic information about the mass. Kern reported that of the 44% of patients (20 of 45) who underwent mammography, studies were negative in 80% (16 of 20). Only one patient (2%) underwent FNA of a breast mass, which proved to be falsely negative. As in palpable masses, the reason for false-negative mammography is related to the increased breast density of younger women, which makes x-ray penetration more difficult.

The impact of false-negative mammograms on the delay in diagnosis was studied by Burns and colleagues. In a group of 80 women with negative mammograms, 50 (63%) presented with palpable breast masses. The negative mammogram resulted in a delay in diagnosis in this group of 1 month to 5.4 years; it averaged 11 months. Burns and associates pointed out the irony that although women were being urged to learn breast self-examination and more than 80% of breast cancers are found on palpation by the patient herself, false-negative mammography was creating delays in diagnosis after patients presented to a physician with a self-discovered breast mass.

Others have also noted the curious anomaly that the introduction of mammography into clinical practice as a technique for the early detection of asymptomatic breast cancer has resulted in delayed diagnosis because of its widespread use as a diagnostic tool in symptomatic women. Max and Klamer noted, in a study of 120 women with breast cancer with an average age of 31 years (range, 22–35 years), that in 7% of women who contacted a physician immediately after the onset of symptoms, the physician delayed for more than 2 months before recommending biopsy. Locklear and Langlands noted that in a study of 735 women with breast cancer, 13% had false-negative mammograms, resulting in a diagnostic delay of 11.2 months, ranging from 2.5 to 48 months. Age played a significant role in the rate of false-negative mammographic results. Of the women with false-negative mammographic results, 73% were premenopausal, compared with 38% in the no-delay group.

Others have reported that delays in diagnosis occur in almost 50% of premenopausal women because of false-negative mammography. Although some authors have argued that it would take 80 biopsies of benign palpable lesions in this age group to detect four misdiagnosed breast cancers, Kern believes it is unlikely that patients will accept these probabilistic arguments as a reason not to seek a timely diagnosis of mammographic abnormalities. Minimally invasive breast biopsy techniques, such as FNA biopsy or ultrasound-guided core biopsy, are accompanied by extremely low morbidity rates. The safety of these approaches negates any arguments suggesting that these types of biopsies are “unnecessary surgery.” Katz and coworkers reported that in a series of women in British Columbia and Washington State, the preponderance of diagnostic delays was the result of nonsuspicious, false-negative mammograms. Tennvall and colleagues demonstrated that women with both negative or inconclusive mammograms and negative FNA cytology of palpable breast masses were found to be 11 years younger than the group with combined positive findings. In these young patients, negative cytology and negative mammography led to extended diagnostic delays. Delays in diagnosis, even when the end result is benign, can have significant adverse psychological impact on patients.

The high rate of false-negative mammograms in young women has led some to recommend that diagnostic mammography simply not be used in symptomatic women. Mahoney and Csima studied 302 women with breast cancer and found 87%, or 263 women, had false-negative mammograms. Mahoney noted that mammography is most productive when used as a routine screening study in women older than 50 years of age with clinically normal breasts. These workers noted that 53% of palpable breast cancers did not image in women younger than 45 years of age. The mean age for a false-negative mammogram with a palpable breast cancer was 49.3 years; for a positive mammogram with a palpable cancer, it was 58 years. The mean size for a negative mammogram was 2.1 cm, and for a positive mammogram, it was 3.3 cm. Mahoney recommended three rules related to mammography and breast cancer: (1) use mammography as a screening study in older women with normal breasts; (2) never delay biopsy of a breast lump that is solid on aspiration because of a negative mammogram; and (3) mammography in symptomatic women younger than 35 years of age is unrewarding and should not be used.

Barratt and coworkers used a telephone survey to evaluate women’s expectations of mammography in a subpopulation of women (n = 115) completing a larger, comprehensive breast health survey (n = 2935). Unrealistically high expectations of the ability of mammography to detect disease were present in these women, many of whom favored litigation despite the known, reported false-negative rate for mammography. Inadequate education on the true ability of mammography to detect disease in a variety of settings and patient age groups is one important contributor to the malpractice problem in breast cancer. Chamot and Perneger came to similar conclusions, suggesting that the patient’s lack of understanding of the ability of mammography to detect breast cancer is one key factor in litigation. The widespread use of mammography in symptomatic breast cancer comes at a high cost, as noted previously. The indemnity cost of misdiagnosed breast cancer, based on errors in mammographic readings, averaged about $230,000 per case in 2005 and had grown to more than $300,000 in 2015.

Langlands and Tiver reviewed 1433 consecutive patients undergoing mammography and found a false-negative rate in those with palpable abnormalities of 30%. In 16% of these patients, the false reassurance of mammography directly contributed to diagnostic delays ranging from 2 to 24 months. Langlands and Tiver used a statistical argument to show that the use of diagnostic mammography in women with a palpable breast lesion of any age is inappropriate for two reasons: (1) the low probability of imaging the lesion in the young and (2) the inability to make definitive statements about a cancer diagnosis without a confirmatory biopsy, even in older women. In this series, diagnostic delays as a result of false-negative mammography ranged from 2 months to 3 years.

Some authors have disputed the rate of false-negative mammography. Cregan and coworkers studied the extent of delay in 219 women and found that only 11% of women had false-negative mammography. This led to a delay in diagnosis of 1 to 3 months in 10% of women (3 of 32 cases). These authors pointed to the value of mammography in women as young as 25 years of age (in whom early signs of familial cancer may be detected, such as irregular, clustered microcalcifications), especially in those with a family history of breast cancer in which early onset is the rule. Bassett and associates argued for a tailored mammographic examination in women younger than 35 years of age with localized breast symptoms, particularly those without a palpable lump. In a study of 1016 women younger than 35 years of age with breast cancer, Bassett evaluated a group of 454 women with palpable breast masses. He noted that two women sustained delays of 4 months and 10 months because mammograms did not image palpable lesions of 2 cm and 1.5 cm; these lesions were labeled as fibroadenomas without biopsy confirmation. In terms of nonlump symptoms in a group of 53 patients, one 34-year-old patient with localized breast tenderness was diagnosed with architectural distortion on tailored mammogram, leading to an immediate breast biopsy and cancer diagnosis. One 26-year-old patient with unilateral discharge had a negative mammogram and sustained a delay of 6 weeks before a biopsy was performed. On the basis of these results, Bassett reminded readers that a negative mammogram should not preclude biopsy of a palpable, solid mass. Blichert-Toft and colleagues in a series of 167 patients in a Danish breast clinic, showed that immediate workup of vague symptoms or unilateral palpable findings by needle aspiration biopsy or open biopsy prevented delayed diagnosis, despite false-negative mammograms in eight patients (5%).

Screening mammograms that show highly suspicious lesions in younger women with no palpable breast abnormalities may diagnose breast cancer with great accuracy and with a detection rate as high as 40%. However, when mammograms are read as nondiagnostic, indeterminate, or not suspicious, the rate of missed cancers approaches 5% (6 of 127). Erickson and colleagues showed that 2% of patients observed because of an indeterminate mammogram, without the presence of symptoms, were later diagnosed as having cancer. Of the 114 women in the study group, 3 sustained delays of 3, 12, and 15 months, respectively. Nonetheless, with an average delay of 10 months, patients had no progression in stage, as measured by the rate of positive axillary nodes.

The introduction of three-dimensional mammography and other computerized techniques to enhance mammographic imaging has resulted in concerns that mammograms read without these advanced technologies might expose radiologists to a greater degree of malpractice risk. However, until such time as advanced methods to computerized or enhance breast imaging is the generally accepted standard of care, the impact of these techniques in reducing the delayed diagnosis of breast cancer, and subsequent litigation, remains unknown.