Of 11 patients with documentation, all were postmenarcheal and thin. Median body mass index (calculated as weight (kg)/[height (m)]2) was 22 (range 19–30). Gynecologic age (years since menarche) was known for six patients, and ranged from 8 to 11 years (median 11 years). No features of anovulation were found (as defined by cycle length 35 days or more, hyperandrogenism, diagnosis of polycystic ovary syndrome or hyperinsulinemia). Three patients had never taken oral contraceptive pills (OCP), six were taking the OCP at diagnosis, and one had taken it in the previous year before diagnosis. No patient had taken hormone replacement therapy. Duration of OCP use ranged from 12 to 36 months (median 19 months). Age of first use was known in only three patients, and the median age was 20 years (range 18–22 years). Eight patients did not smoke tobacco. The three who did had a history of smoking one pack per day for 3–5 years.
Six patients were parous, four of whom had been diagnosed with breast carcinoma during or soon after pregnancy. One patient with stage I disease was diagnosed with breast carcinoma during her third pregnancy at 12 weeks of gestation, and another with stage IV disease was diagnosed 2 months after giving birth to her first child. At 28 weeks of gestation, she was diagnosed with hemolysis, elevated liver enzymes, low platelets syndrome and renal obstruction. Postpartum she was found to have rectosigmoid obstruction and biopsy of a pelvic mass 2 months postpartum was compatible with a breast carcinoma primary. She did not have a palpable breast mass. One patient with stage IIIa disease was diagnosed 7 months after her second delivery. She presented 2 months postpartum with breast pain and a breast mass and was initially diagnosed with mastitis. The fourth patient, who had stage IIIb disease, was diagnosed 8 months postpartum after noticing a 7-cm lump while breastfeeding, associated with asymmetry and a bloody discharge. Median age of first delivery for the six patients was 22.5 years (range 17–29 years).
Of these 11 patients, two had a strong family history of breast cancer (defined as at least one first-degree relative with breast cancer before the age of 50 years or two or more relatives with breast cancer, at least one a first-degree relative). Six patients had a weak family history of breast cancer (defined as any lesser degree of family history of breast cancer). Three had no family history of breast cancer. Nine patients had a positive family history for any malignancy. No patients were tested for genetic mutation. One patient had a prior diagnosis of malignancy (Hodgkin lymphoma, diagnosed and treated with mantle and abdominal radiotherapy 5 years before presentation with breast carcinoma). No other patients received prior radiotherapy or chemotherapy. Two patients had a history of fibrocystic change before diagnosis, but the rest did not have any previous known breast disease.
The time from onset of symptoms to presentation was 0.8 months (or 26 days; range 0.1 to 3 months). Time between presentation and biopsy diagnosis was 1.1 months (range 0–16 months). Time between onset of symptoms and biopsy diagnosis was 3 months (range 0.2–19 months). Reasons for delayed biopsy beyond 1 month after presentation are summarized in Table 5.
Only 2 of the 11 young women had a suspected diagnosis of breast carcinoma after the initial clinical history and examination. Of the two, one patient had a history of Hodgkin lymphoma. The other patient was 24 years of age with a weak family history but had a visible 4-cm hard breast mass with an irregular edge.
Biopsy diagnosis was most commonly performed by wide local excision or lumpectomy. A positive diagnosis for malignancy was made in three of five patients who had a breast ultrasonography performed (sensitivity, 60%), four of six patients who had mammography performed (sensitivity, 66%), one patient who had a computerized tomographic scan of the breast, one of two patients who had fine needle aspiration cytology performed (50% sensitivity), and in both of the two patients who had core needle biopsy performed (sensitivity, 100%). One patient with bloody nipple discharge had a ductogram, which was negative.
We evaluated known factors that may lend support to management with surgical excisional biopsy in young women who present with a breast mass (Table 6). All 11 patients with known clinical presentation had at least one suspicious feature identified on initial clinical history, examination, or imaging. Two patients had one suspicious feature, four had two suspicious features, two had three, one had four, and two had six.
Patients were treated with a combination of surgery, chemotherapy, and radiotherapy. Eight were treated by mastectomy, one had lumpectomy followed by wide local excision, and one had lumpectomy and axillary node dissection. The patient with widely metastatic disease had palliative care only. Of the 10 patients who had surgery, all had adjuvant chemotherapy except one patient with stage 1a disease; four had adjuvant radiation. Three patients (one with stage I disease and a history of Hodgkin lymphoma, and others with stage IIIa and IIIb disease) had both regional and local recurrences 11–25 months after original diagnosis (median 19 months) that were managed with local surgery, chemotherapy, and radiotherapy. Two patients had other malignancies diagnosed after original diagnosis. One patient had a contralateral breast cancer diagnosed 11 years after original diagnosis, and stage III ovarian carcinoma diagnosed 19 years after original diagnosis. Another patient had a contralateral breast carcinoma diagnosed 2 years after original diagnosis. Median duration of clinical follow-up from biopsy diagnosis was 25.5 months (range 0–371 months). Median duration of follow-up by any means was 44.5 months (range 0–371 months). At time of last follow-up, four patients had died from disease, one had died from disseminated ovarian carcinoma, five were alive with no evidence of disease, and two were alive with disease. Eight patients had duration of follow-up for at least 5 years. All of those with stage I (2/2) and II disease (2/2) were alive at 5 years, whereas no patients with stage III (0/3) or IV disease (0/1) were alive at 5 years. Overall 5-year survival was 50%.
Breast masses are common in young women and mostly benign.5,16–18 In one clinical study, 3.2% of young women presenting for any reason were found on physical examination to have a breast mass.16 In a retrospective review of 185 surgically treated breast masses occurring in adolescent patients at the Mayo Clinic, 2.6% (4 cases) were malignant: a primary rhabdomyosarcoma, a metastatic rhabdomyosarcoma, a metastatic neuroblastoma, and one case of non-Hodgkin lymphoma.5 Similarly, in another study of 178 breast masses in patients aged 20 years or younger, no carcinomas were found.19 Dehner et al17 found one case of breast cancer in a review of 374 breast masses in patients younger than 20 years of age, and Corpron et al12 reported 10 cases of infiltrating carcinoma (nine ductal, one lobular) in 16 patients 13–19 years of age referred to M. D. Anderson Cancer Center with malignant breast masses.
This 70-year population-based study confirms that breast carcinoma in young women is rare. Similarly, between 1992 to 2002, data from the Surveillance, Epidemiology and End Results (SEER) database demonstrated the age-adjusted incidence rate of breast cancer in white girls and women under the age of 25 years to be 1.7 per million person-years in 15- to 19-year-olds and 12.0 per million for 20- to 24-year-olds. Corresponding figures for African American young women are 3.4 and 24.8 per million.20
The overall 5-year relative survival for 2001–2007 from 17 SEER geographic areas for women of all ages with breast cancer was 89%, with survival being 99% for localized disease, 84% for disease with regional spread, and 23% for metastatic disease.9 In contrast, survival for younger women with breast cancer is less favorable.21 Poorer survival, in young patients, could be related to reduced screening, more aggressive disease, and delayed diagnosis. Seventy percent of women older than 40 years participate in screening mammography,22 resulting in earlier disease detection. Consequently, the proportion of breast cancer patients who present with a palpable mass has declined from 70% in 1983 to 44%.23,24 In the year 2000 at our institution, 57% of breast cancers treated with surgery were screen-detected. Median age of patients was 60 years, median tumor size was 1.5 cm; invasive ductal carcinoma was present in 60%; and stage I, II, and III cancers were detected in 46%, 33%, and 4%, respectively.24
A study of more than 1 million women with breast cancer recorded in the American College of Surgeons Cancer Database between 1998 and 2005 demonstrated that women younger than 40 years of age were more likely to present with more advanced (stage III or IV) disease (20% compared with 13.5%), and they were more likely to have infiltrating ductal carcinoma (76.9 compared with 67.9), as did the patients in this study.25 Furthermore, younger women still have significantly poorer survival even after adjusting for stage, histology, and grade.26
We found that delayed diagnosis in young women results from delayed presentation and biopsy, similar to other reports.12 Pregnancy may have been a contributing factor as also described in previous reports,27 although in one patient diagnosed at 12 weeks of gestation the antenatal visit may have afforded an opportunity for a breast examination not otherwise scheduled. Sensitivity of mammograms and ultrasound examinations has been reported as 55% and 58%, respectively, attributed to the nodularity of breast tissue.10 Most patients in this study did not undergo imaging or core biopsy, as these diagnostic techniques were not commonly used during the entire period of observation of the study. Of the 11 patients in whom clinical presentation was known, all had at least one concerning feature on original clinical history that required consideration of immediate biopsy.
The triple test (palpation, ultrasound examination by an experienced breast imager, and core needle biopsy) is currently considered the gold standard for evaluation of breast masses in women younger than 30 years.10 Excisional biopsy is now reserved for the patient in whom the core needle is nondiagnostic; when there is discordance among the pathology, physical examination, and radiologic appearance; or for patients who will not tolerate a core needle biopsy, such as younger patients under age 18 years. There is growing evidence that core needle biopsy is not routinely required in evaluation of breast masses in young women, except where metastatic disease is suspected.5 In a review of 357 patients aged 25 years or younger with a breast mass consistent with a fibroadenoma on ultrasound scan, 0.8% were found to have a benign phyllodes tumor, 0.3% had a breast carcinoma, and the rest had benign disease.28 Furthermore, phyllodes tumors may display heterogeneity on histologic assessment, and needle biopsy alone may be indeterminate.29 Our report did not identify any patients younger than 18 years with breast cancer. It has been the authors' practice and recommendation that small, discrete, mobile breast masses in teenagers undergo clinical with or without ultrasound surveillance, unless there are concerning clinical features or features on imaging that would warrant surgical excision regardless.2,3 In Box 1, we propose criteria for either surgical excisional biopsy or interim core needle biopsy, which may be a useful tool in the evaluation of a young woman with a breast mass. Around 10% of patients under 40 years with breast cancer harbor a BRCA1 or BRCA2 mutation,30 and those older than 18 years would also be offered genetic testing; the benefits of testing in adolescent women are not as clearly established.31
The limitations of this study include the fact that it does not evaluate the incidence of all breast masses in the study population and so we cannot comment on the relative frequency of metastases or stromal tumors in the breast. Because only evaluation data on patients with breast cancer are reported, no comment can be made about the specificity of clinical findings and diagnostic imaging modalities for breast masses in young women. The findings may not be generalizable to all young women, because the Olmsted County study population was 98% white and mainly of non-Hispanic ethnicity, and the observations span several decades.
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© 2011 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
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