Local recurrence after breast conserving surgery in breast cancer

The general aim of this thesis was to gain increased insight into the problem of local recurrences after breast conserving surgery for breast cancer. In a population-based cohort of 4,694 women with invasive breast cancer, operated in 1981 to 1990 and followed through 1997, we studied how breast conserving surgery had been adopted into clinical practice. As adoption became more widespread, the indications for this type of surgery broadened. A simultaneous moderate impairment of the results was noted. Generally, the risk of local recurrence was higher than expected, but the estimated survival rates were gratifying. The overall risk of local recurrence was 9.2% at five years and 21.1% at ten years, and the breast cancer-specific survival was 93.3% and 85.2% at five and ten years, respectively. A large proportion of the women had non- protocol treatment; nearly 30% were not given radiotherapy.

Prognosis and prognostic factors after a local recurrence in the breast were studied in 391 women from a population-based cohort of 6,613 women. The prognosis differed notably between the different subgroups of breast recurrences, the subgroups being defined by time to and location of recurrence. Radiotherapy prevented or delayed the appearance of a local recurrence, but had little influence on the breast cancer-specific survival in women who experienced a local recurrence. The strongest independent prognostic factors for breast cancer-specific survival were time to local recurrence and Nottingham Prognostic Index.

In the cohort of 6,613 women, 92 women experienced a local recurrence in the axilla. The overall risk of axillary recurrence in the cohort was 1.0% at five years and 1.7% at ten years. The major risk factors for axillary recurrence were low age, large tumour size and minor or no axillary surgery, while radiotherapy to the breast reduced the risk of axillary recurrence. The breast cancer-specific survival after axillary recurrence was poor, 59.2% and 43.5% at five and ten years, respectively.

In an analysis of risk factors for local recurrence including 491 cases and 1,098 controls from a cohort of 7,502 women with invasive or non-invasive breast cancer, multivariate analysis showed low age, multicentricity and unclear/unknown surgical margins to be associated with an increased risk of local recurrence, while radiotherapy to the breast and adjuvant hormonal therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer. Nottingham Histologic Grade and Nottingham Prognostic Index were not helpful in determining the risk of local recurrence.

The time relation between local recurrences and distant metastases was studied in a cohort of 5,496 women with invasive breast cancers. Women who had experienced a local recurrence had a higher hazard rate of distant metastases than women with no local recurrence, and the hazard rate curve showed two peaks, at three and seven years after the primary operation. In women with early breast cancer who had experienced a local recurrence, the second peak represented approximately half of the documented distant metastases, and may be explained by dissemination from the local recurrences.

List of scientific papers

I. Fredriksson I, Liljegren G, Arnesson LG, Emdin SO, Palm-Sjovall M, Fornander T, Frisell J, Holmberg L (2001). Time trends in the results of breast conservation in 4694 women. Eur J Cancer. 37(12): 1537-44.
https://pubmed.ncbi.nlm.nih.gov/11506963

II. Fredriksson I, Liljegren G, Arnesson L, Emdin S, Palm-Sjovall M, Fornander T, Holmqvist M, Holmberg L, Frisell J (2002). Local recurrence in the breast after conservative surgery-a study of prognosis and prognostic factors in 391 women. Eur J Cancer. 38(14): 1860-70.
https://pubmed.ncbi.nlm.nih.gov/12204668

III. Fredriksson I, Liljegren G, Arnesson LG, Emdin SO, Palm-Sjovall M, Fornander T, Holmqvist M, Holmberg L, Frisell J (2002). Consequences of axillary recurrence after conservative breast surgery. Br J Surg. 89(7): 902-8.
https://pubmed.ncbi.nlm.nih.gov/12081741

IV. Fredriksson I, Liljegren G, Palm-Sjovall M, Arnesson LG, Emdin SO, Fornander T, Lindgren A, Nordgren H, Idvall I, Holmqvist M, Holmberg L, Frisell J (2002). Risk factors for local recurrence after breast conserving surgery. [Submitted]

V. Fredriksson I, Blomqvist C, Holmqvist M, Frisell J, Holmberg L (2002). Local recurrence in breast cancer - a cause of dissemination and death? [Manuscript]