Study Confirms Association Between Cancers of Breast, Thyroid

Miriam E Tucker

January 22, 2016

The likelihood of thyroid cancer (TC) and breast cancer (BC) occurring in the same woman are greater than would occur by chance, a new study suggests.

The findings, from a retrospective case-control single-center study, were published in the December 2015 issue of Thyroid by Jee Hyun An, MD, PhD, of Seoul National University College of Medicine, South Korea, and colleagues.

In the study, 4.3% of TC patients subsequently developed BC, and 2.6% of BC patients later were found to have TC, both rates more than twice as high as the expected rates of each cancer in the general population.

Some of the increase is likely due to greater surveillance among women who already had one cancer. However, expression of both estrogen and progesterone receptors was significantly higher in the tissues of BC patients with coexisting TC compared with those who had only BC, suggesting that a specific molecular pathogenesis might underlie the association, Dr An and colleagues argue.

Clinically, they say, the findings suggest that regular breast examination — as recommended for the general population — should be emphasized in women with TC. However, because there were no clinical predictors of TC development among the BC patients compared with those with TC alone and no evidence of improved prognosis for early TC diagnosis, "screening for TC in BC patients cannot be recommended, irrespective of the patient's age at BC diagnosis."

Asked to comment, Jennifer H Kuo, MD, director of the thyroid biopsy program and the endocrine surgery research program at Columbia University, New York, told Medscape Medical News that the findings generally align with previous studies, including her own on both TC following BC and BC after TC.

"This is a single-institution retrospective study evaluating the link between breast cancer and thyroid cancer....Their findings more or less corroborate findings from previous, similar studies — that there is a connection between the two diseases; the higher incidence goes beyond what you would expect from pure surveillance; second malignancies develop an average of 5 years from the first; and the cancers that result tend to be small, nonaggressive, [estrogen-receptor/progesterone-receptor–positive] tumors. Unfortunately, it still does not provide an answer to the etiology of this connection, which is likely to be multifold."

With regard to screening recommendations, Dr Kuo said, "I do in general advocate for screening for these diseases. However, the biggest resistance comes from screening breast-cancer survivors for thyroid cancer. There is an overdiagnosis of thyroid cancer in general, and the pendulum is swinging to be less aggressive in its treatment, as reflected in the new American Thyroid Association guidelines published last year. I advocate for screening, but cautiously.

"I think that in general the evidence is out there that breast and thyroid cancer are connected….There should be more of an effort now to identify what the cause of this association is," she told Medscape Medical News,

Comparing Cancers

The study population included 4243 female patients first diagnosed with primary papillary or follicular TC who underwent total thyroidectomy and 6833 with primary BC who had curative surgery. Of those, 181 were diagnosed with the other cancer over the 40-year study period (1970–2009), including 4.3% of the TC group and 2.6% of the BC patients.

A total of 55 patients had TC followed by BC, 81 had BC first and then developed TC, and 45 had concomitant disease, defined as having both diagnoses within 2 years of one another (of whom the majority had TC identified incidentally during diagnosis of BC).

Those groups were matched 1:3 with controls who only had just one or the other cancer within the same time periods, matched for age at diagnosis and time of surgery.

Among the TC-first/BC-second group, the breast cancers were significantly more likely to be ductal carcinoma in situ (DCIS), at 29%, than in either the BC-first/TC-second (10%) or the concurrent-TC/BC group (10%) and less likely to be infiltrative ductal carcinoma (69% vs 86.5% and 80%, respectively).

Expression of both estrogen and progesterone receptors was significantly higher in the groups with concurrent TC and BC (82% estrogen-receptor expression) and with TC first/BC second (89%) compared with the BC-first/TC-second group (68%), suggesting that receptor signaling might represent common etiological factors in the development of both cancers, the authors speculate.

Breast Cancer Following Thyroid Cancer

The mean latency from diagnosis with TC to the development of BC was 5.2 years.

In patients with TC, BC development was greater than in the general population, with a standardized incidence ratio of 2.45.

Since the increased incidence of BC following TC might be attributable to the incidental detection of BC during follow-up of TC or to frequent health checkups following TC (especially in the cases detected within 5 years), Dr An and colleagues excluded cases that were incidentally detected by imaging during medical follow-up of TC. This reduced the standardized incidence ratio, but to a still-significant 2.16.

Comparing the 55 patients in the TC-first/BC-second group with their 165 matched controls, mean age at diagnosis of BC, median duration of follow-up after diagnosis with BC, and family history of BC were similar between the two groups. However, the percentage of DCIS was significantly higher (29.1% vs 8.5%, P < .05), and tumor size was smaller (1.7 vs 2.5 cm, P < .05).

Patients who had BC within 5 years following TC also had smaller tumor sizes, a higher proportion of DCIS, and a lower recurrence rate compared with those who developed BC after more than 5 years. The expression of estrogen and progesterone receptors did not differ between those who developed BC within 5 years of TC or later but were significantly higher in both subgroups compared with the controls (P < .05).

Between the TC-first/BC-second patients and their controls, there were no differences in family history of TC, histological type, tumor size, lymph nodes and distant metastasis, multifocality, extrathyroidal extension, tumor recurrence, and radioactive-iodine therapy, regardless of the time to detection of BC.

Thyroid Cancer Following Breast Cancer: No Clinical Predictors

The mean latency from BC to the development of TC was 5.9 years, and the standardized incidence ratio was 2.18 compared with TC in the general population. After exclusion of cases incidentally detected by imaging performed for BC follow-up, the incidence ratio was reduced but still significant, at 1.73.

The incidence of second primary TC was significantly higher within the first 5 years of BC diagnosis and then decreased over time (P < .01).

Similar to the TC-first/BC-second group, the detection rate of TC in the process of a medical checkup and health screening was relatively higher within 5 years after the diagnosis of BC.

Compared with their control group, those diagnosed with TC within 3 years of BC had smaller tumors (1.5 vs 2.0 cm) but did not differ in mean age at diagnosis, TC tumor type (more than 90% were papillary thyroid cancer for both), tumor size, lymph-node positivity, distant metastasis, multifocality, extrathyroidal extension, and recurrence rate (4.9% vs 6.2%), suggesting no clinical predictors for TC development, Dr An and colleagues note.

Expression of both estrogen and progesterone receptors was significantly higher in the BC-first/TC-second group compared with controls (68% vs. 55% for estrogen receptors), and these results were similar regardless of time between the two diagnoses.

In addition to the possibility that hormone receptors may play a role in the pathogenesis of TC as they do in BC, the effect of treatment for either cancer may also play a role, the authors note.

Neither the study authors nor Dr Kuo have relevant financial relationships.

Thyroid. 2015;25;1330-1337. Abstract

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